237 results for "study_type:"exome sequencing" AND repository:ega"

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• Mechanism of action and resistance to Trastuzumab Deruxtecan in patients with metastatic breast cancer: the DAISY trial

  Study EGAS00001006905

• Germline variants in childhood cutaneous melanoma

  Study EGAS00001006995

• Targeted exome DNA sequencing analysis of POETIC Good/Poor Responders to aromatase inhibitors based on change in Ki67

  Study EGAS00001007303

• Detection of somatic mutations of angioimmunoblastic T-cell lymphoma

  Study EGAS00001007333

• Mechanism of action and resistance to Trastuzumab Deruxtecan in patients with metastatic breast cancer

  Study EGAS00001007372

• EuroTARGET is a European study on mRCC, collecting clinical data, germline DNA, and tumor samples.

  For patients with metastatic renal cell cancer (mRCC), treatment choice is mainly based on clinical parameters. With many treatments available and the limited response to treatment and associated toxicities, there is much interest in identifying better biomarkers for personalized treatment. EuroTARGET aims to identify and characterize host- and tumor-related biomarkers for prediction of response to tyrosine kinase inhibitor therapy in mRCC. Here, we describe the EuroTARGET mRCC patient cohort.

  Study EGAS50000000798

• Whole exome sequencing of pre-invasive lung adenocarcinoma in non-smokers

  The prevalence of lung adenocarcinoma (LUAD) has increased sharply in East Asia. Early diagnosis leads to better survival rates, but this requires an improved understanding of the molecular changes during early tumorigenesis, particularly in non-smokers. We performed whole exome-sequencing and RNA-sequencing for samples from 94 East Asian patients with precancerous lesions (25 with atypical adenomatous hyperplasia [AAH]; 69 with adenocarcinoma in situ [AIS]) and 73 patients with early invasive lesions (minimally invasive adenocarcinoma [MIA]). Cellular analysis revealed that the activities of endothelial and stromal cells could categorize tumors into molecular subtypes within pathology-defined lesion types. These subtypes were linked with the advanced radiology-defined lesion type and coordinated with immune cell infiltration throughout the progression of LUAD. Characterization of these lesion types identified positively selected mutation patterns, and suggested that angiogenesis of the late-stage AIS type potentially contributes to tissue invasion of the MIA type. Our findings offer a novel resource that may help to improve early diagnosis and patient prognosis, and also suggest possible approaches for early disease interception.

  Study EGAS50000000438

• Understanding Rare Variant Contributions to autism: Lessons from Dystrofin-Deficient Model

  This project generated a whole-exome sequencing (WES) dataset of 83 boys with a pathogenic variant in the DMD gene, along with WES data from the parents of 38 of them, totaling 159 samples. Pathogenic DMD variants, besides causing dystrophinopathies, are also known risk factors for neurodevelopmental disorders (NDDs). However, the low penetrance of NDDs in individuals with dystrophinopathies suggests that additional factors contribute to their manifestation. This study aimed to: (1) characterize ASD in males with dystrophinopathies; (2) determine the relevance of additional de novo and inherited rare risk variants for their neurodevelopmental phenotype; and (3) clinically and functionally characterize the identified risk variants.

  Study EGAS50000000754

• Genomic analysis of head and neck squamous cell carcinoma upon acquired resistance to cetuximab

  Anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (cetuximab) remain the only FDA-approved targeted therapy for patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). Unfortunately, most patients develop acquired resistance to cetuximab and there is currently no further therapeutic option for these patients (unmet clinical need), thereby highlighting the need to better understand resistance-causing mechanisms. Here, we carried out whole-exome sequencing on 2 cetuximab-sensitive and -resistant patient-derived xenograft models of HNSCC. Our data reveal several genetic alterations (mutations and copy number variations) associated with acquired resistance to anti-EGFR therapy.

  Study EGAS50000000800

• Longitudinal evaluation of circulating tumor DNA in early breast cancer receiving neoadjuvant systemic therapy using a tumor-informed assay

  This study evaluates a highly sensitive tumor-informed ctDNA assay in a real-world cohort of patients receiving neoadjuvant therapy (NAT) to assess clinical validity and explores prognostic outcomes

  Study EGAS50000000771

• Surgery in combination with immune checkpoint therapy as an effective treatment for patients with metastatic cancer.

  Abstract Surgical removal of primary tumors was shown to reverse tumor-mediated immune suppression in pre-clinical models with metastatic disease. However, how cytoreductive surgery in the metastatic setting modulates the immune responses in patients, especially in the context of immune checkpoint therapy (ICT)-containing treatments is not understood. Here, we report the first prospective, non-comparative clinical trial (N=104) using three different ICT-containing strategies plus cytoreductive or “debulking” surgery to remove the primary tumor-bearing kidney or a metastatic lesion as a treatment for patients (N=43) with metastatic clear cell renal cell carcinoma (mccRCC). For those patients (N=61) who were not candidates for cytoreductive surgery, a biopsy was obtained instead for correlative biological studies. Our data demonstrated that the combination of ICT with cytoreductive surgery was safe and feasible in patients with mccRCC. The 2-year overall survival was 84% with a median OS of 54.7 months for patients who received ICT containing regimens plus surgery. Immune-monitoring studies with co-detection by indexing (CODEX) identified distinct tumor spatial conformation of cellular subsets as a novel and improved predictor of response to ICT. Importantly, single-cell RNA-sequencing data demonstrated that surgical removal of the tumor increased antigen-presenting dendritic cell population with a concurrent reduction in KDM6B expressing immune-suppressive myeloid cells in the peripheral blood. Together, this study highlighted the feasibility of combining ICT with cytoreductive surgery in a metastatic setting and demonstrated potential enhancement of immune responses following ICT plus cytoreductive surgery in patients with metastatic disease.

  Study EGAS00001005667

• Whole-exome sequencing profiling of patients with metastatic prostate cancer at VHIO

  Metastatic prostate cancer (mPC) is enriched for homologous recombination repair (HRR) gene alterations, which have prognostic and predictive value. Routine clinical implementation of next-generation sequencing (NGS) is still limited. We investigated the association between genomic and functional loss of HRR, using NGS and a RAD51 immunofluorescence (RAD51-IF) iprimary or metastatic biopsies from patients with stage IV prostate cancer. Whole-exome sequencing was pursued for paired tumor-normal samples.

  Study EGAS50000000736

• Next-generation molecular analysis of surgical margins in oral squamous cell carcinoma for assessment of microscopic residual disease and personalized postoperative treatment decision

  Background : Patients operated for an early oral squamous cell carcinoma (OSCC) with clear margins have a 5-year local relapse rate of around 15%. Assessing the microscopic residual disease (MRD) remains a challenge. In a phase II prospective trial, we evaluated the tetranucleotide microsatellite instability markers in the surgical margins in T1-T2 OSCC resected with pathologically clear margins. Goal : Detect MRD in surgical margins and adapt the postoperative decision-making Details : Whole exome sequencing (WES) on early oral squamous cell carcinoma (OSCC) with clear margins, and on resection margins, 86 patients with a median follow-up of 58 months (range 30.4-83 months)

  Study EGAS50000000823

• WES samples of patients with anti-PD-1 resistant HNSCC from a non-randomized, open-label phase 1b clinical trial

  Immune checkpoint blockade (ICB) is an effective treatment for a subset of patients with head and neck squamous cell carcinoma (HNSCC); however, the majority remain refractory. In a nonrandomized, open-label Phase 1b clinical trial, participants with recurrent and/or metastatic (R/M) HNSCC who had progressed on ICB were treated with low-dose 5-azacytidine (5-aza) daily for either 5 or 10 days, in combination with durvalumab and tremelimumab. The primary objective was to determine the biologically effective dose of 5-aza. In this study, whole exome sequencing (WES) was performed on baseline samples from 12 participants, and genomic alterations were analyzed to access the genetic background of these participants.

  Study EGAS50000000729

• Identification of phenotype-modifier genes

  Patients were stratified at the extremes of the renal phenotype according to their estimated glomerular filtration rate annual decline and subjected to whole exome sequencing (WES) aiming to find candidate phenotype-modifier genes.

  Study EGAS50000000829

• WES of der(1;7)(q10;p10) myeloid neoplasms

  The study examined WES of der(1;7)(q10;p10) myeloid neoplasm cases. BAM files of WES of 26 myeloid neoplasm patients with der(1;7)(q10;p10) were used to identify key driver genes in patients with der(1;7)(q10;p10). This study is one of the largest WES for der(1;7)(q10;p10)(+) myeloid neoplasm cases.

  Study EGAS50000000704

• Genetic subtyping by Whole Exome Sequencing across Diffuse Large B Cell Lymphoma and Plasmablastic Lymphoma.

  99 FFPE derived tumor tissue DNA, 9 circulating tumor DNA samples and 38 paired germline DNA were used. A library containing whole exome regions was used to isolate the DNA for sequencing (SureSelect XT Human All Exon V6 (Agilent technologies)). Sequencing on a NovaSeq 6000 instrument (Illumina, paired end, 2x100, mean 566Gb per FlowCell) at the National Genomic Analysis Center (CNAG, Barcelona, Spain) was performed.

  Study EGAS50000000371

• Mutational Profile in Newly Diagnosed Diffuse Large B-Cell Lymphoma: GAINED Study

  The GAINED study (NCT01659099) is a randomized phase 3 trial comparing obinutuzumab (G) to rituximab (R) in combination with ACVBP or CHOP14 induction, followed by PET-guided consolidation. This post-hoc analysis focuses on primary mediastinal B-cell lymphoma (PMBL) patients, confirmed through expert pathological review and characterized using gene-expression profiling (GEP) and Next-Generation Sequencing (NGS)

  Study EGAS50000000929

• McQuillin_Global_WES_Schizophrenia

  Whole Exome Sequencing of Schizophrenia cases and matched controls performed at the Broad Institute on a cohort from UCL, London, UK

  Study EGAS50000000901

• Cohort B germline exome sequencing

  Cohort B includes IDH-wild type, EGFR amplified, surgically derived glioblastoma tissue samples from male and female individuals. Germline DNA was isolated from whole blood.

  Study EGAS50000000951

• Cohort A germline exome sequencing

  Cohort A includes glioma tumors of varied grading and pathology from male and female individuals. Germline DNA was isolated from whole blood.

  Study EGAS50000000952

• Cohort B tumor exome sequencing

  Cohort B includes IDH-wild type, EGFR amplified, surgically derived glioblastoma tissue samples from male and female individuals. Tumor DNA was isolated from FFPE tissue. Both tumor and germline DNA are present for each sample in the overall dataset.

  Study EGAS50000000955

• The Genomic Map of Poland in Open Access

  The main goal is to prepare and share WGS/WES of Polish population In this project NGS (next generation sequencing) was performed using Illumina NOVASEQ 6000 and Illumina DRAGEN aligner was used. Shared BAM and BAM.BAI files Library Construction Protocol: Illumina DNA PCR-Free Prep, Tagmentation. Reference Genome: GRCh37.

  Study EGAS50000000096

• The phase II Neo-Pembro trial: neoadjuvant pembrolizumab in stage IV high-grade serous ovarian cancer

  While immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, their efficacy in high-grade serous ovarian cancer (HGSOC) remains limited. Nevertheless, some patients achieve lasting responses, emphasizing the need to understand how the tumor microenvironment and molecular characteristics influence ICI response. We hypothesized higher efficacy of ICI when used in the neoadjuvant setting and preceded by induction chemotherapy. The phase 2 Neo-Pembro study (NCT03126812) included 33 untreated patients with stage IV HGSOC who were planned for 6 cycles of carboplatin-paclitaxel and interval cytoreductive surgery. Pembrolizumab (pembro) was added from cycle two and continued for one year. The primary objective was to assess intratumoral immune activation, through multiplexed immunofluorescence and immune-related gene expression. Our data provide evidence of immune activation, characterized by an increase in CD3+, CD8+, CD8+/FOXP3+ ratio, and TNF-α and interferon-γ signaling, and was most evident in major pathologic responders, which were 9/33 patients (27%, 95%CI 14-46) at time of surgery. Pathologic response was strongly associated with overall survival. At a median follow-up of 52.8 months, 8/9 major responders were alive, including 6 patients without recurrence, and 4 of 24 minor responders were alive, including one patient without recurrence. PD-L1 expression and homologous recombination deficiency were predictive of major response and may serve as potential biomarkers, warranting further exploration. In a post-hoc comparison, major responders treated with pembro had significantly better overall survival than major responders in a historic cohort treated without pembro. Our data indicate that immune activation was stronger in the subset of major pathologic responders and these patients may derive long-term survival benefits from the addition of neoadjuvant pembro.

  Study EGAS50000000781

• PRPH2-Related Retinal Dystrophies: Mutational Spectrum in 103 Families from a Spanish Cohort

  Various NGS experiments from patients affected by genomic variants at gene PRPH2, one of the most frequently inherited retinal dystrophy (IRD)-causing genes.

  Study EGAS50000000847

• Tumor mutational landscape in individuals with CMMRD

  Whole exome sequencing data from the tumors (n=16) of individuals with constitutional mismatch repair deficiency. Data was aligned to GRCh38.

  Study EGAS50000000081

• Analysis of CD20 loss in patients treated with Mosunetuzumab

  CD20 is an established therapeutic target in B-cell malignancies. The CD20xCD3 bispecific antibody mosunetuzumab has significant efficacy in B-cell non-Hodgkin lymphomas (NHL). Since target antigen loss is a recognized mechanism of resistance, we evaluated the contribution of CD20 expression to clinical response in patients with relapsed and/or refractory NHL in the phase 1/2 GO29781 trial (ClinicalTrials.gov: NCT02500407) investigating mosunetuzumab monotherapy. CD20 was studied using immunohistochemistry (IHC), RNA sequencing, and whole-exome sequencing performed centrally in biopsies collected prior to treatment, or as paired samples at pre-dose and on-treatment, or at-progression. Prior to treatment, most patients exhibited a high proportion of tumor cells expressing CD20; however, the proportion of CD20+ tumor cells in 14/293 (6%) patients was <10%. Analyses of paired biopsies from patients during treatment revealed that CD20 levels were maintained in 29/30 (97%), vs patients with samples at-progression, in which 11/32 (34%) showed CD20 loss. Reduced transcription or acquisition of truncating mutations explained most but not all cases of CD20 loss. In vitro modeling confirmed the effect of CD20 variants identified in clinical samples on reduction of CD20 expression and confirmed missense mutations in the extracellular domain that could block mosunetuzumab binding. This study expands knowledge about the occurrence of target antigen loss after anti-CD20 therapeutics to CD20-targeting bispecific antibodies and elucidates the underlying mechanisms for reduced CD20 expression at disease progression that may be generalizable to other anti-CD20 targeting agents. These results also establish the utility of readily-available IHC staining for CD20 as a tool to inform clinical decisions.

  Study EGAS50000000151

• WES of paired gDNAs and PPGL tumor DNA from patients with CCHD-PPGL.

  WES of paired germline DNA (12) and PPGL tumor DNA (14) from peripheral blood/saliva and formalin-fixed paraffin-embedded (FFPE) blocks from surgery, respectively, from patients with congenital heart disease (CCHD) and pheochromocytoma and paraganglioma (PPGL).

  Study EGAS50000000815

• Identification of IQCH as a calmodulin-associated protein required for sperm motility in humans

  Study EGAS00001007423

• Lung cancer Early Molecular Assessment

  This study aimed to validate the potential utility of a clinically accessible, highly sensitive tumor-informed circulating tumor DNA (ctDNA) assay. The study considers a ‘landmark’ time period (between two weeks and four months after definitive treatment), as well as longitudinal sampling (>2 weeks) and compares two independent, retrospectively collected real-world cohorts.

  Study EGAS50000000896

• Genomic Profiling of an anti-PD-L1 treated cohort of Newly Diagnosed GBM patients

  Checkpoint inhibitor therapy has limited efficacy in the outcomes of patients with glioblastoma (GBM). This study involves whole exome sequencing of newly diagnosed glioblastoma patients treated with concurrent atezolizumab, radiation therapy, and temozolomide. By analyzing 29 tumor-normal pairs, the study aims to explore the correlation between tumor genomics and the efficacy of PD-L1 blockade treatment outcomes and further identify which patients may benefit more from such therapy.

  Study EGAS50000000783

• Autosomal dominant macular dystrophy associated with THRB: identification of new families and variants 

  This study aims to refine the ophthalmologic phenotype, report a novel THRB variant, and investigate the impact of these splicing variants at the protein level.

  Study EGAS50000000861

• Whole Exome Sequencing of a Lung Adenocarcinoma Patient Across Three Time Points

  A 65-year-old female patient with a significant smoking history (40 pack-years) was first diagnosed with lung adenocarcinoma (LUAD) in the left lung in May 2020 (L1-T1). One year later, in May 2021, the patient progressed with a new LUAD in the right lung (L1-T2) and in May 2024, another LUAD emerged in the right lung (L1-T3). Whole Exome Sequencing (WES) analysis was conducted on three tumor biopsies obtained at different time points from the same patient to investigate clonal trajectories.

  Study EGAS50000000812

• Medulloblastoma WES

  WES for tumor and normal samples

  Study EGAS50000000261

• Cohort A tumor exome sequencing

  Cohort A includes glioma tumors of varied grading and pathology from male and female individuals. Tumor DNA was isolated from fresh frozen tissue.

  Study EGAS50000000949

• Mesenchymal niche in myelodysplastic hematopoiesis at single cell resolution

  Study EGAS00001007568

• Whole Exome Sequencing Data of indolent primary renal B-Cell lymphomas

  We used sequenced 34 iNHL samples using whole exome sequencing (WES) data to evaluate possible mutational signatures and driver mutations associated with the patient’s clinical and cytogenetic characteristics.

  Study EGAS50000000774

• Whole exome sequencing of prDLBCL

  To investigate the mutational landscape of prDLBCL, 34 cases were selected for whole exome sequencing.

  Study EGAS50000000403

• Coding and regulatory somatic profiling of triple-negative breast cancer in Sub-Saharan African patients

  The burden of triple-negative breast cancer (TNBC) may be shaped by genetic factors, particularly inherited and somatic mutation profiles. However, data on this topic remain limited, especially for the African continent, where a higher TNBC incidence is observed. In the age of precision medicine, cataloguing TNBC diversity in African patients becomes imperative. We performed whole exome sequencing, including untranslated regions, on 30 samples from Angola and Cape Verde, which allowed to ascertain on potential regulatory mutations in TNBC for the first time. A high somatic burden was observed for the African cohort, with 86% of variants being so far unreported. Recurring to predictive functional algorithms, 17% of the somatic single nucleotide variants were predicted to be deleterious at the protein level, and 20% overlapped with candidate cis-regulatory elements controlling gene expression. Several of these somatic functionally-impactful mutations and copy number variation (mainly in 1q, 8q, 6 and 10p) occur in known BC- and all cancer-driver genes, enriched for several cancer mechanisms, including response to radiation and related DNA repair mechanisms. TP53 is the top of these known BC-driver genes, but our results identified possible novel TNBC driver genes that may play a main role in the African context, as TTN, CEACAM7, DEFB132, COPZ2 and GAS1. These findings emphasize the need to expand cancer omics screenings across the African continent, the region of the globe with highest genomic diversity, accelerating the discovery of new somatic mutations and cancer-related pathways.

  Study EGAS50000001013

• PRADO trial - Personalized response-directed surgery and adjuvant therapy after neoadjuvant ipilimumab plus nivolumab in stage III melanoma

  The PRADO trial tested a personalized response-directed treatment approach based on the pathologic response after neoadjuvant ipilimumab plus nivolumab in stage III melanoma patients. In patients achieving a major pathologic response, in their index lymph node (the largest lymph node metastasis at baseline), therapeutic lymph node dissection (TLND) and adjuvant therapy were omitted. Patients with partial response underwent TLND only, whereas patients with pathologic non-response underwent TLND and adjuvant systemic therapy ± synchronous radiotherapy.

  Study EGAS50000000268

• Localised colon cancer WES study contaning WBCs, tissue and plasma samples at different time points

  Decision-making based on circulating tumor DNA (ctDNA) status following curative-intent surgery in stage II-III colon cancer (CC) is where the strongest clinical evidence lies. Commercial or academic assays are predominantly used to detect ctDNA, aiming to reveal minimal residual disease (MRD) and identify patients at high risk of recurrence. However, while current tests demonstrate exceptional specificity in detecting MRD among patients who later experience recurrence, their sensitivity is notably limited, particularly immediately after surgery when decisions regarding ACT are crucial. Additionally, up to 70% of patients with stage II-III colon cancer fail to clear ctDNA after standard adjuvant treatment (ACT) and subsequently experience recurrence. In this study, we performed whole exome sequencing (WES) of ctDNA at different timepoints in relapsed CC patients using two independent cohorts, alongside transcriptomic and proteomic analyses of metastases to gain a deeper understanding of progression mechanisms. An assay based on a tumor-agnostic approach from WES could enhance sensitivity in detecting MRD disease compared to current assays. Immune evasion appears to be the primary driver of progression in the localized CC setting, facilitated by a functional mutational burden at relapse. This suggests that immunotherapy could extend its efficacy to patients with microsatellite stability, broadening treatment options. Moreover, organoid modeling affirms the promising potential of targeted therapy to surpass conventional treatments in eradicating MRD.

  Study EGAS50000000204

• WXS Normal Samples Javelin head and neck 100

  Study EGAS00001007526

• Exome sequencing study of cells derived from QHJI14s04 human iPSC secondary cell stock

  Genomic abnormalities of cells used in regenerative medicine should be checked. This study evaluates variants on coding sequences of cells derived from QHJI14s04 human iPSC secondary cell stock. Here we conducted whole exome sequence of three vials from the stock.

  Study EGAS50000000934

• WXS Tumor Samples Javelin head and neck 100

  Study EGAS00001007583

• Germline WES of serrated polyposis syndrome

  The serrated polyposis syndrome (SPS) is a disease with a mainly unknown inherited genetic basis characterized by the presence of multiple and/or large serrated polyps in the colon and a higher associated risk for colorectal cancer (CRC). The objective of the present study was to identify new SPS/CRC germline predisposition genes by using whole-exome sequencing in two affected SPS patients from the same family.

  Study EGAS50000000765

• ACUITI

  This study assessed the feasibility and performance of a tumor-informed circulating tumor DNA (ctDNA) assay in patients with metastatic HR+/HER2- breast cancer receiving endocrine therapy and CDK4/6 inhibitors.

  Study EGAS50000000962

• IDH- and H3-wildtype high-grade gliomas in teenagers and young adults

  Whole exome sequencing of high grade gliomas occurring in teenagers and young adults between the ages of 13 and 30. This study combines methylation array profiling, whole exome sequencing and fusion panels sequencing to provide and integrated diagnosis of tumours in this age group.

  Study EGAS50000000641

• WES - Characterization of a Breast Patient-derived Tumor Organoid biobank from an underserved population of patients.

  EXaCT-2, an augmented WES assay, has been performed on a cohort of 4 patients and their corresponding organoids

  Study EGAS50000000684

• Sensitive neoantigen discovery by real-time mutanome-guided immunopeptidomics - WES

  Targeting cancer-specific HLA-peptide complexes is a promising immunotherapy approach, with mutated neoantigens offering high value for their immunogenicity and cancer-specificity. Selecting immunogenic targets requires personalized prioritization of cancer-specific immunopeptides. Mass spectrometry (MS)-based immunopeptidomics supports this process by directly identifying cancer-specific antigens and informing global presentation patterns to refine immunogenicity predictions. Clinical pipelines, however, must balance global depth and target sensitivity compounded by low input samples and time constraints. Here, we present NeoDiscMS, an extension of the NeoDisc pipeline, enabling personalized immunopeptidomics data acquisition. By leveraging real-time NGS-guided spectral acquisitions, NeoDiscMS maximizing sensitivity with minimal loss of global depth. NeoDiscMS improves TAA-derived peptide detection up to 20% and enhances neoantigen identification confidence compared to the clinical gold standard method. Designed for effectiveness and ease of use, it requires minimal effort for implementation. NeoDiscMS advances personalization in clinical antigen discovery by enabling more sensitive neoantigen detection while seamlessly integrating into existing workflows.

  Study EGAS50000000976

• Whole Exome Sequencing of Human Gastro-esophageal Cancer PDXs

  The current study investigates biomarkers of response to anti-EGFR therapies in gastro-esophageal cancer. Whole exome sequencing was performed on 26 tumors to explore potential factors influencing treatment outcomes. As part of the analysis, somatic mutations in EGFR, ERBB2, and key downstream signaling genes (KRAS and PIK3CA) were examined to exclude the presence of known mutations conferring sensitivity/resistance. The study aims to contribute to the identification of patients who may benefit from lower-toxicity regimens, improving treatment personalization and minimizing adverse effects.

  Study EGAS50000000966

• Expanding the SPTBN1 Spectrum: A Case of Neurodevelopmental Disorder with GI and Musculoskeletal Involvement

  Background: Mutations in the SPTBN1 gene, which encodes the βII-spectrin protein, are associated with a recently described neurodevelopmental syndrome characterized by developmental delay, intellectual disability, autistic traits, seizures, and dysmorphic features. While the phenotypic spectrum continues to evolve, gastrointestinal (GI) involvement and vertical transmission remain rarely reported features. Case Presentation: We describe a 13-year-old male from Georgia with a heterozygous missense mutation in SPTBN1 (c.3799C>G, p.Leu1267Val), inherited from his clinically unaffected mother. The patient presented with cognitive and motor delays, autistic traits, behavioral challenges, feeding difficulties, growth delay, musculoskeletal anomalies (pectus excavatum, pes planus), and persistent GI symptoms including abdominal pain and gallbladder sludge. Despite therapy with ursodeoxycholic acid and nutritional counseling, the gallbladder abnormalities persisted over a 12-month follow-up. Feeding therapy could not be initiated due to access barriers, although parental efforts led to modest dietary improvement. Upon recent visit pes planus was also confirmed. Conclusion: This case contributes to the growing body of literature on SPTBN1-related neurodevelopmental disorders, highlighting the potential for a broader phenotypic spectrum than currently recognized. In addition to the well-documented behavioral, cognitive, and musculoskeletal features, our patient presented with notable gastrointestinal involvement—specifically, gallbladder sludge and feeding disorder—which are not commonly reported in association with SPTBN1 mutations. Although causality cannot be established from a single case, the observed GI manifestations may be indirectly related to underlying neurobehavioral features such as ASD and associated eating disorders. The identification of a vertically transmitted missense variant (c.3799C>G, p.Leu1267Val) adds to the limited but growing evidence of inherited SPTBN1 mutations, expanding our understanding of transmission patterns. Given the novelty of the findings, we emphasize the need for multidisciplinary management, including feeding and behavioral therapy, as well as longitudinal follow-up to assess developmental, nutritional, and hepatobiliary outcomes. Future studies and case series are warranted to determine whether pes planus, pectus excavatum, gastrointestinal symptoms, including biliary tract involvement, represent an underrecognized component of the SPTBN1 phenotypic spectrum.

  Study EGAS50000001213

• Acute lymphoblastic leukemia in children produces endogenous T-cells targeting tumor associated antigens and neoantigens in peripheral blood

  In this study we investigated the presence of endogenous T-cells recognizing private tumor-associated antigens and predicted neoantigens. To this end, HLA-I and HLA-II restricted tumor associated antigens (TAAs) and neoantigens were respectively identified and predicted from matched tumor and germline (PBMCs) in three acute lymphoblastic leukemia patients. Circulating T-cells targeting both Mass spectrometry (MS)-identified TAAs and predicted neoantigens were identified in virtually all pediatric BCP-ALL patients, extending up to two years on remission.

  Study EGAS50000000925

• PEVOsq

  The PEVOData PEVOsq basket trial is an open-label, multi-center, phase II trial investigating the combination of pembrolizumab (an immune checkpoint inhibitor) with vorinostat (a histone deacetylase inhibitor). This trial focuses on treating patients with recurrent or metastatic squamous carcinomas, including cancers of the cervix, head and neck, anus, vulva/vagina, penis, and lung. The aim is to evaluate the efficacy and safety of this combination, with pembrolizumab administered every 3 weeks and vorinostat daily. Outcomes include overall response rate and progression-free survival.

  Study EGAS50000000731

• Germline variants in UHRF1 are associated with multi-locus imprinting disturbance in humans and mice

  Genomic imprinting provides is an epigenetic process crucial for normal development and is disrupted in congenital imprinting disorders(CIDs). There is great interest in the clinical consequences and aetiology of multilocus imprinting disturbance(MLID) which occurs in some individuals with CID, though the cause of MLID is unknown in most cases. We investigated a kindred with a CID and MLID and identified a rare genetic variant in the UHRF1 gene which has a critical role in the establishment and maintenance of DNA methylation. We generated a mouse model and found that the equivalent Uhrf1 variant was associated with prenatal lethality and disruption of normal imprinting mechanisms. These findings support UHRF1 as a novel candidate gene for CIDs with MLID.

  Study EGAS50000001179

• Whole Exome Sequencing of Waldenström Macroglobulinemia (WM) Precursor Conditions

  In this study we aimed to comprehensively characterize the genomic landscape of WM precursor conditions and identify potential biomarkers of progression to symptomatic WM by means of Whole Exome Sequencing (WES) of CD19-selected samples from 139 patients, primarily with IgM-MGUS and asymptomatic WM. Overall, our study shows that genomic profiling of patients’ tumor at the time of aWM diagnosis might represent an improved strategy for identifying patients at high risk to progression who could benefit from earlier intervention.

  Study EGAS50000001249

• Response to tumor-infiltrating lymphocyte adoptive therapy is associated with preexisting CD8+ T-myeloid cell networks in melanoma

  Adoptive cell therapy (ACT) using ex vivo–expanded tumor-infiltrating lymphocytes (TILs) can eliminate or shrink metastatic melanoma, but its long-term efficacy remains limited to a fraction of patients. Using longitudinal samples from 13 patients with metastatic melanoma treated with TIL-ACT in a phase 1 clinical study, we interrogated cellular states within the tumor microenvironment (TME) and their interactions. We performed bulk and single-cell RNA sequencing, whole-exome sequencing, and spatial proteomic analyses in pre- and post-ACT tumor tissues, finding that ACT responders exhibited higher basal tumor cell–intrinsic immunogenicity and mutational burden. Compared with nonresponders, CD8+ TILs exhibited increased cytotoxicity, exhaustion, and costimulation, whereas myeloid cells had increased type I interferon signaling in responders. Cell-cell interaction prediction analyses corroborated by spatial neighborhood analyses revealed that responders had rich baseline intratumoral and stromal tumor–reactive T cell networks with activated myeloid populations. Successful TIL-ACT therapy further reprogrammed the myeloid compartment and increased TIL-myeloid networks. Our systematic target discovery study identifies potential T-myeloid cell network–based biomarkers that could improve patient selection and guide the design of ACT clinical trials.

  Study EGAS50000001217

• WES-based association study of cefaclor-induced anaphylaxis

  This study investigates the genetic factors associated with cefaclor-induced anaphylaxis using whole-exome sequencing (WES).

  Study EGAS50000001163

• Excised DNA Circles from V(D)J Recombination Promote Relapsed Leukaemia

  In this study, we show that ESCs replicate and persist through many cell generations. High ESC copies at diagnosis of BCP-ALL strongly correlate with subsequent relapse. These data provide the first demonstration that the V(D)J recombination by-product, when replicated to elevated levels, potently associates with the V(D)J recombinase to cause adverse disease outcomes.

  Study EGAS50000001043

• Exome Sequencing of familial and sporadic Meniere disease patients

  This study aims to characterize the genetic architecture of spanish patients diagnosed with Meniere disease (MD), focusing on both familial (FMD) and sporadic (SMD) forms, by analyzing coding variants. Whole-exome sequencing was performed on these patients, and variants were called and annotated using the nf-core/sarek bioinformatics pipeline, including alignment to the GRCh38 reference genome. The resulting data provide a curated resource for investigating the potential genetic contribution to the pathophysiology of MD. All data will be made available for reuse under controlled access.

  Study EGAS50000001178

• Exome sequencing for identifying point mutations driving M haemophilum susceptibility

  To understand non tuberculous Mycobacterial susceptibility

  Study EGAS50000001076

• Disease recurrence after pathologic response (Recurrence DNAseq)

  In this study we aim to gain insight into the mechanisms of immune evasion after initial pathologic response to neoadjuvant immune checkpoint inhibition in macroscopic stage III melanoma by pooling data of the neoadjuvant OpACIN, OpACIN-neo and PRADO trials(EGAD00001012116, EGAS00001004832, EGAD00001006730, EGAS50000000268). Therefore we analyzed in-depth paired baseline(n=10) and recurrent tumor samples of the lymph nodes(n=10) and brain metastasis (n=2) through Whole Exome Sequencing (WES) analyses. Additionally we incorporated transcriptome sequencing data from 22 patients (21 paired-end samples and one single end sample)

  Study EGAS50000000488

• TRACERx NSCLC - Whole exome multiregion sequencing data

  Study EGAS00001006494

• Integrated drug screening and molecular profiling in pediatric AML

  This study aims at identifiying functional-genomic predictors of patient risk in pediatric AML by performing image-based drug response profiling and comprehensive molecular profiling on primary pediatric AML samples

  Study EGAS50000001083

• Whole Exome Sequencing of Bipolar cases and matched controls performed at the Broad Institute on a cohort from Cardiff, UK (Owen)

  Study EGAS00001005855

• Lessons learned from the exome sequencing of nine cases of infertility and the way forward

  This study investigated the role of exome sequencing in the diagnosis of male and female infertility. Nine unrelated cases referred between 2019 and 2024 were analysed using exome sequencing, with segregation confirmed by Sanger sequencing and functional assays for splicing variants. We identified nine causative variants in genes including TUBB8, PATL2, CCDC39, STAG3, KIAA0319, FBXO43, AGBL5/BBS7, PLCZ1, and HS6ST1, six of which were novel. The findings highlight diverse reproductive phenotypes such as oocyte maturation arrest, early embryonic arrest, spermatogenic failure, and syndromic infertility. This work demonstrates the value of combining genetic, functional, and clinical approaches to improve diagnostic yield and patient care in reproductive failure.

  Study EGAS50000001320

• Germline WES-data of pediatric cancer patients with variants in HBOC-related genes

  This study focused on the identification of (likely) pathogenic germline variants (LP/PV) in 25 adult-onset HBOC-related genes in a cohort of 372 pediatric cancer patients. The cohort was sequenced on Illumina platforms. The files uploaded here belong to the 27 individuals with such a LP/PV.

  Study EGAS50000001073

• ICARUS-BREAST01-ExomeSeq

  Efficacy, safety and biomarker analysis of ICARUS-BREAST01: a phase 2 Study of Patritumab Deruxtecan in patients with HR+/HER2- advanced breast cancer. Whole-exome sequencing (WES) is available for 43 tumor samples and 43 blood samples collected at entry into the trial.

  Study EGAS50000000542

• Whole-exome variant calling of individuals from the study of familial pulmonary fibrosis in the Canary Islands

  Research study of rare genetic variants associated with familial cases of pulmonary fibrosis in patients and relatives from Canary Islands, Spain.

  Study EGAS50000000782

• Genetic differences between primary colorectal cancer and its paired synchronous and metachronous metastases

  In this study we present for the first time the genetic differences associated with different chronicity of colorectal cancer liver metastases identified by whole-exome sequencing of 210 CRC samples. We focus on differences in primary tumors as we hypothesize that these are the cause of the differences in the time course of the disease. The results suggest that distinct tumor progression pathways account for different chronicity outcomes with ultimate impact on patient’s prognosis

  Study EGAS50000000996

• Identification of putative multiple myeloma (MM) susceptibility genes

  We sought to identify novel MM susceptibility genes using a collection of families with multiple cases of MM/MGUS, including 189 affected individuals from 40 families, and index cases from an additional 88 families, along with 170 early-onset (EO) MM cases (≤ 55 years). We analyzed a total of 347 affected individuals using whole exome (N=321) and whole genome (N=26) sequencing. Samples were identified and collected through nation-wide efforts in France, Sweden and Greece. We focused on rare (MAF<0.5%) germline protein truncating and likely deleterious missense variants in genes harboring variants in at least two families showing variant-disease segregation, and in additional index (≥2) and/or early-onset (≥2) cases.

  Study EGAS50000001259

• Whole exome sequencing of bladder tumors

  Bladder carcinomas are immunogenic, and patients with bladder cancer benefit from immune checkpoint therapy. This is correlated to a high tumor mutation burden, which provides a higher number of neoepitopes that can be recognized by tumor-specific CD8+ T cells. Intravesical Bacillus Calmette-Guérin (BCG) is used to treat non-muscle invasive bladder cancer (NMIBC), but its mechanism of action remains elusive. Most lymphocytes appearing in the urine of BCG-treated patients are CD4+ T cells though preclinical studies showed that CD8+ T cells are also necessary for BCG treatment efficacy. It is currently unknown which proportion of patients with non-metastatic bladder cancer develop a spontaneous antitumor CD8+ response, and if BCG treatment influences this response. were prepared using the xGen Dual Index UMI Adapters (IDT), and genomic DNA (gDNA) extracted (DNeasy kit, Qiagen) from formalin-fixed paraffin- embedded (FFPE) or snap-frozen tumor tissue, as well as autologous lymphocytes. Libraries were subjected to paired-end sequencing using Illumina HiSeq4000 with a coverage depth of 250X. Library preparation was carried out with the AllType FASTplex NGS 11 Loci Flex Kit (One Lambda), and sequencing was conducted on the Illumina MiSeq platform.

  Study EGAS50000001248

• WES analysis of paired tumor and non-tumoral DNA of 4 patients with non-muscle-invasive bladder cancer

  We performed WES of tumor DNA and non-tumoral DNA (extracted from PBMC) of 4 patients with non-muscle invasive bladder cancer, who after the tumor resection went on to receive BCG treatment as they had high-risk disease. In order to identify tumor-specific mutations that could give rise to patient-specific neo-epitopes, we performed paired WES of tumor and non-tumoral DNA for each patient. For patient UC2, 3 different tumors were resected at the same time and DNA from these 3 tumors were sent separately for WES.

  Study EGAS50000001382

• Prevalence and association of microsatellite instability and Lynch syndrome Pan-Cancer and development of a personalized cancer risk prediction tool for Lynch syndrome carriers in India

  The study aimed to systematically study MSI/ MMRd status in tumour DNA and germline mutations in mismatch repair (MMR) genes across a unique, large and heterogeneous group of commonly observed non-colorectal gastrointestinal and genitourinary tumours in the Indian population.

  Study EGAS50000001449

• Molecular profiles in early onset prostate cancer

  Paired germline (blood) and tumour samples were collected from prostate cancer cases <65 years at diagnosis to identify genetic changes in early onset prostate cancer.  Whole exome sequencing was performed on these samples. The aim was to determine if these changes are associated with more aggressive disease and to identify targets for treatment and screening by identifying associations with family history, DNA repair germline mutations, and clinical features.

  Study EGAS50000001467

• Phylogenetic analysis of paired breast carcinomas identifies genetic events associated with clonal recurrence and invasive progression

  Development of ipsilateral breast carcinoma following diagnosis of breast ductal carcinoma in situ (DCIS) has been assumed to represent recurrence of the primary tumour. However, this may not be the case and it is important to know how often recurrences are new tumours. Ipsilateral primary-recurrence pairs (n=78) were sequenced to test their clonal relatedness. Shared genetic events were identified from whole exome sequencing (n=54 pairs) using haplotype-specific copy number and phylogenetic analysis. The remaining pairs were sequenced by a targeted panel or low-coverage whole genome sequencing. We included 32 non-recurrent DCIS to compare recurrent and non-recurrent disease. We found that 7% of DCIS recurrences were non-clonal by whole exome sequencing, indicative of a new breast carcinoma. Lower resolution methods detected a higher non-clonality rate (29%). Comparing primary DCIS with their recurrences found that evolution of DCIS to invasive disease was associated with increased ploidy and copy number events. TP53 mutations were enriched in DCIS with clonal recurrence compared with non-recurrent DCIS. Our results verify that de novo “recurrent tumours” of independent origin occur in patients who may be at high risk. (https://www.biorxiv.org/content/10.1101/2024.05.19.594731v2.full)

  Study EGAS50000001298

• WES sequencing of metastatic colorectal cancer patient-derived xenografts with known response to irinotecan.

  Chemotherapy is the standard-of-care treatment for metastatic colorectal cancer (mCRC) and benefits some patients, but what distinguishes responders from non-responders is unclear. In this study, we expand a pre-existing collection (https://doi.org/10.1158/2159-8290.CD-24-0556) of molecularly annotated patient-derived xenografts to uncover functional predictors of response to 5-FU and irinotecan combination therapy (FOLFIRI) in mCRC. We complemented previous mutational profiles with whole exome sequencing for 46 xenografts with known response to irinotecan.

  Study EGAS50000001484

• Neoadjuvant immune checkpoint blockade in mismatch-repair proficient colon cancers

  Immune checkpoint blockade has led to paradigm shifts in the treatment of various tumour types, yet limited efficacy has been observed in patients with metastatic mismatch-repair proficient (pMMR) colorectal cancer. Here we report an in-depth analysis of patients with early-stage pMMR colon cancer from the phase II NICHE study (ClinicalTrials.gov: NCT03026140). A total of 31 patients received neoadjuvant treatment of nivolumab plus ipilimumab followed by surgery. The response rate was 26% and included six patients with a major pathological response (≤10% residual viable tumour). One patient with an ongoing clinical complete response did not undergo surgery. Responses were observed despite a low tumour mutational burden in all tumours, while chromosomal genomic instability scores were significantly higher in responders compared to non-responders. Responding tumours were more likely to be TP53 mutant, KRASG12 wildtype and had significantly higher baseline expression of proliferation signatures and TCF1. Imaging mass cytometry also revealed a higher percentage of Ki-67+ cancer and Ki-67+ CD8+ T cells in responders compared to non-responders. Meanwhile, in non-responders, we observed an enrichment for an inflamed-fibrotic microenvironment associated with TGF-β expression, hinting towards possible resistance mechanisms. These results provide a comprehensive analysis of response to neoadjuvant ICB in early-stage pMMR colon cancers and identify potential biomarkers for patient selection.

  Study EGAS50000000856

• NAR-GAB 2025 deposit data

  Human exome gVCFs: rare-disease cohort for the NAR-GAB 2025 study on splicing-SNV prioritization.

  Study EGAS50000001456

• Identification of New Therapeutic Targets for Renal Medullary Carcinoma via Integrated Genomic and Transcriptomic Profiling

  Renal medullary carcinoma (RMC) is a rare, aggressive kidney cancer associated with sickle cell trait, characterized by SMARCB1 loss and resistance to conventional therapies used for other renal cell carcinomas (RCC). We conducted whole exome sequencing (WES) on RMC samples. This study provides a large molecular characterization of RMC, highlighting TROP2 and other cell surface markers as promising therapeutic targets.

  Study EGAS50000001280

• Variability in immune response genes and prediction of severe SARS-CoV-2 infection (INMUNGEN-Cov2 project)

  Genetic factors may contribute to explain the variable clinical response to SARS-CoV-2 infection. To this end we sequenced the DNA of 392 COVID-19 patients from Spain. Whole Exome Sequencing (WES) was performed at two different sequencing centers. Half of the samples were sequenced at a commercial service, NIMGenetics, whereas the other half were sequenced by the EASI-Genomics consortium. Finally, Variant Call Format (VCF) files for each sample was also obtained.

  Study EGAS50000000066

• Genomic Data from Patients with Advanced Rare Cancers Treated with Pembrolizumab

  Rare cancers lack effective evidence-based treatments despite contributing substantially to cancer-related mortality. The goal of this study is to identify molecular biomarkers associated with response to pembrolizumab in patients with advanced rare cancers.This dataset includes genomic profiling generated from patients enrolled in an investigator-initiated phase II basket trial of pembrolizumab.

  Study EGAS50000001508

• ERDERA Diagnostic Research Workstream - WES reanalysis (distributed approach)

  The ERDERA Diagnostic Research Workstream – WES reanalysis (distributed approach) aims to improve diagnostic yield by systematically reanalyzing existing whole exome sequencing (WES) data from rare disease cases. The goal is to apply updated bioinformatics pipelines, novel variant interpretation tools, and the latest reference databases to detect clinically relevant variants that may have been missed in earlier analyses. By using a distributed approach across multiple expert groups, the project fosters collaborative interpretation and knowledge sharing to enhance diagnostic outcomes for patients.

  Study EGAS50000001514

• Whole Exome Sequencing of monomorphic epitheliotropic intestinal T-cell lymphoma and enteropathy associated T-cell lymphoma

  Background : Enteropathy-associated T-cell lymphoma (EATL) and monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) are aggressive malignancies with limited treatment options and poor prognosis. Our research on MEITL has uncovered its genetic portrait including hallmark SEDT2 mutations, expanded its pathological spectrum, and identified molecular biomarkers influencing patients’ outcome. In this study, we aimed to establish and clarify the similar and diverging features of EATL. Methods : A large combined cohort of patients with EATL (n=30) and MEITL (n=52) was assembled and tumor samples were used for whole-exome and RNA sequencing profiling.

  Study EGAS50000001126

• A human induced pluripotent stem cell toolbox for studying sex chromosome effects-Whole exome seq

  To generate autosomaly isogenic hiPSCs with various chromosome complement, we use Klinefelter syndrome patient skin fibroblasts. These cells harbour XXY sex chromosomes, which can be lost during the reprogramming event and generate cells which are autosomaly identical to each other but differ in sex chromosome complement. We use state of the art reprogramming methods to generate panels of isogenic XXY, XX and XY iPSCs from XXY patient fibroblasts. We have performed Whole exome sequencing on Klinefelter syndrome patient's skin fibroblasts in order to check if two X chromosomes are identical and to see if we can distinguish which X chromosome is more likely to be lost during the reprogramming event in XY cell lines.

  Study EGAS50000000930

• WES of Mino-VEN-R Mantle Cell Lymphoma Cells

  This project investigates the genetic basis of therapy resistance in mantle cell lymphoma (MCL) using whole exome sequencing (WES) of the Mino_VEN_R cell line, a model of resistance to pirtobrutinib, a non-covalent BTK inhibitor. Our study suggested that drug-tolerant persister (DTP) cells evade therapy through metabolic and phenotypic reprogramming. By analyzing the exome profile of resistant cells, this study aims to identify mutations associated with treatment escape and cellular plasticity. The findings will contribute to a better understanding of resistance mechanisms and support the development of more effective therapeutic strategies.

  Study EGAS50000001088

• Using Exome-sequencing to characterize the resistance to lirafugratinib

  We characterized resistance to lirafugratinib with whole exome sequencing in patients with FGFR2-driven cancers, treated in the phase 1/2 ReFocus trial (NCT04526106) and enrolled in the UNLOCK program at Gustave Roussy

  Study EGAS50000001371

• Rare germline variants in patients with personal and family history of colorectal cancer

  A double primary colorectal cancer (CRC) in a familial setting signals a high risk of CRC. In order to find novel high/moderate penetrance CRC susceptibility genes, we performed whole-exome sequencing on germline blood samples of seven familial cases from Poland with a double primary CRC.

  Study EGAS50000000606

• Heritable pulmonary arterial hypertension - new genetic findings and environmental triggers

  Whole exome seqeuncing data were analysed for a total of 13 family members of five heritable pulmonary arterial hypertension (HPAH) families to identify a disease causing variant. In a first step, variants only present in affected family members and absent in healthy relatives of the respective family were selected. Subseqeuntly, due to incomplete penetrance of genes in PAH, the analysis was extended to variants present both in affected and healthy individuals. Heterozygous variants were primarily investigated followed by homozygous, compound heterozygous, and bi-allelic variants of interest. This study led to the identification of rare deleterious variants in three out of five families.

  Study EGAS50000001275

• Whole-exome sequencing identifies new pathogenic germline variants in patients with colorectal polyposis

  Adenomatous polyposis confers an increased risk of colorectal cancer development. Here, we investigated probably underlying predisposition variants in patients with suspected colorectal polyposis without variants in APC and MUTYH genes by whole exome sequencing (WES). Twenty-seven patients were included and subjected to germline WES. After filtering out variants for sequencing quality, variant allele fraction frequency, and population frequency, variants were manually prioritized by the ACMG criteria. Among the variants identified, 17 were classified as pathogenic or likely pathogenic (in 12 patients). This study gives information of probably associated polyposis variants in Brazilian patients without germline pathogenic variants in APC and MUTYH genes, supporting the utilization of next-generation sequencing for screening in these patients beyond these genes.

  Study EGAS50000000591

• Common origin and somatic mutation patterns of composite lymphomas and leukemias

  When two lymphomas occur concurrently or sequentially in a patient, it is a major question whether they derive from the same lymphocyte or hematopoietic precursor cell or developed independently. We studied four composite classic Hodgkin lymphomas (HL) and other mature B-cell lymphomas, and two composite mature B- and T-cell neoplasias by whole exome sequencing (WES) and analyzed shared somatic mutations in the lymphomas of these clonally related composite lymphomas, indicating their derivation from a common, pre-malignant precursor. Most identified mutations were restricted to one or the other of these lymphomas, likely explaining how distinct lymphomas developed from a common ancestral B cell. In the two B-cell/T-cell lymphoma cases, and a composite clonally unrelated HL/chronic lymphocytic leukemia, the lymphoma partners did not share any somatic mutations. In three cases, we identified potentially oncogenic variants also in cells serving as constitutional controls.

  Study EGAS50000001017

• Tracing the molecular route to progression in miRNA biogenesis-defective thyroid lesions

  Alterations in the DICER1 and DGCR8 microprocessor genes confer risk to the development of benign and malignant thyroid lesions. The involvement of 2 miRNA biogenesis genes in benign and malignant thyroid tumors highlights the key role of miRNAs in the thyroid gland. We traced the progression from benignity to malignancy in DICER1- and DGCR8-mutated thyroid lesions by performing a multiomic characterization of these lesions aiming to uncover unique features characterizing either form for potential use as biomarkers. This multiomic characterization included whole exome sequencing (WES) (N=18), miRNA profiling (N=38), spatial transcriptomics (N=2) and/or methylome (N=281).

  Study EGAS50000001577

• Exome sequencing in HIV+ Viremic Non-Progressors (VNPs) and HIV+ Progressors

  Viremic Non-Progressors (VNPs) maintain normal CD4+ T-cell counts despite uncontrolled HIV-1 replication, but mechanisms leading to CD4+ T-cell preservation are incompletely characterized. We aim to generate a comprehensive understanding of this infrequent phenotype by comparing rates of cellular infection, immunophenotype, genomics, single-cell transcriptomics, metabolomics, and levels of plasma biomarkers in 16 VNPs and 29 HIV+ Progressors. During chronic infection VNPs show lower frequency of HIV-1-infected cells in periphery, which is associated with reduced CCR5 expression and higher prevalence of CCR5Δ32 heterozygosity. The CD8+ T-cell compartment displays a less cytotoxic and less activated phenotype in VNPs. Moreover, despite similar viremia, we found lower bystander CD4+ T-cell death in the VNPs, together with weaker IFN responses, reduced plasma levels of zonulin (a biomarker of intestinal permeability), altered tryptophan catabolism, and preserved LPS responsiveness in vitro. Overall, a complex multifactorial mechanism, suggesting gut-associated lymphoid tissue preservation, underlies resistance to HIV pathogenesis in VNPs.

  Study EGAS50000000079

• Discordant_Monozygotic_Twins_ALS(Genetics)

  Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Regarding genetic factors, pathogenetic mutations in more than 35 genes have been identified as playing a role in disease pathogenesis. However, a substantial portion of ALS heritability remains unaccounted for, pointing to the potential involvement of additional genetic and epigenetic factors. For this reason, we conducted a multi-omics study on a monozygotic twin pair discordant for amyotrophic lateral sclerosis, performing whole exome sequencing, transcriptomic and epigenetic analyses to gain crucial insights into underlying pathogenetic disease mechanisms. Here, we share genetic data.

  Study EGAS50000000908

• Targeted sequencing (paired) of HR genes in primary and metastatic patient-derived xenografts (PDXs) of colorectal cancer (CRC)

  Chemotherapy is the standard-of-care treatment for metastatic colorectal cancer (mCRC) and benefits some patients, but what distinguishes responders from non-responders is unclear. In this study, we leveraged a comprehensive collection of 69 molecularly annotated patient-derived xenografts to uncover functional predictors of response to 5-FU and irinotecan combination therapy (FOLFIRI) in mCRC. Genetic analyses revealed that treatment sensitivity was marked by genomic scars indicative of BRCAness, suggesting homologous recombination (HR) deficiency as a key determinant. Accordingly, we surveyed a manually curated panel of 44 genes with a documented role in HR for the potential presence of pathogenic mutations. We did not observe a specific enrichment of HR gene mutations based on response to FOLFIRI. This result, combined with the absence of widespread biallelic inactivation of the analyzed genes and the predominance of mutations categorized as variants of unknown significance, suggests that FOLFIRI sensitivity is not primarily governed by underlying mutations in HR genes responsible for mitigating the genotoxic effects of this therapeutic regimen.

  Study EGAS50000000075

• Targeted Sequencing Xenturion

  Study EGAS00001006697

• Rare Germline Variants in CDKN2A-Negative Children and Adolescents with Cutaneous Melanoma

  Cutaneous melanoma is a complex disease influenced by both environmental and genetic factors. Inherited susceptibility plays a significant role, involving a combination of high-, intermediate-, and low-penetrance genes. Melanoma in children and adolescents has been speculated to have a stronger genetic component due to the early onset. This study investigates germline variants in early-onset melanoma through exome sequencing of 154 patients in Australia diagnosed with cutaneous melanoma before the age of 20.

  Study EGAS50000001311

• Multiplexed biomarkers dynamically detect heterogeneous residual neuroblastoma cell clone activity in the bone marrow niche

  Our objective was to develop a patient-specific, genomics-informed minimal residual disease (MRD) monitoring strategy for pediatric high-risk neuroblastoma using individualized multiplexed mediator-probe PCR (MP-PCR) assays. Tumor-specific somatic mutations or structural variants were identified through hybrid-capture panel sequencing. We examined tumor material from 8 patients, including 11 primary tumor samples, 3 of which represent spatially distinct primary tumor samples and 2 samples obtained at relapse. Provided are FASTQ data files, bam and bambai files, as well as breakpoint spanning and encompassing read (enspan) bam and bambai files. Sequencing bam data files are aligned to GRCh37.p13 reference genome (processed). Sequencing data were aligned to the GRCh37.p13 reference genome and processed using validated pipelines.

  Study EGAS50000001581

• Whole-exome sequencing (WES) analysis of untreated head and neck cancer patient-derived xenografts (PDXs) matched patient tumor tissue and normal mucosa tissue.

  WES analysis was performed on untreated patient tumor/normal mucosa tissue and matched patient-derived xenograft (PDX) models of primary head and neck squamous cell carcinoma (HNSCC) to investigate the preservation of tumor-specific genomic alterations in the in vivo context.

  Study EGAS50000001622

• Optimized large-scale longitudinal biorepository of gastroesophageal adenocarcinoma patient-derived organoids

  To enable translation studies we created patient derived models to assess biomarkers, target validation, and patient response. To evaluate that the PDOs retain the genomic characteristics of the primary tumours we performed (WES) sequencing of 11 matched primary tumours and their matched organoid samples (total n=22). Libraries were sequenced using Illumina NovaSeq technology. Reads were aligned with BWA alignment to hg38. Files were processed following GATK best practices (version GATK 4.2.3.0). Variants were called using Mutect2. The dataset contains the alignmnent files (.bam) and the called mutations (.vcf).

  Study EGAS50000001614

• The DIRECT study: A roadmap for ctDNA-based risk prediction, molecular profiling and MRD detection in Diffuse Large B Cell Lymphoma

  DIRECT was a prospective, multisite study assessing the feasibility and utility of circulating tumor DNA (ctDNA) in 188 patients with aggressive B-cell non-Hodgkin lymphoma using capture panel sequencing and an open-source computational pipeline. The aims of the study were 1)baseline risk stratification, 2)genetic profiling and 3)ultrasensitive minimal residual disease (MRD) assessment. This study highlighted the considerable potential, but also the caveats and limitations, of ctDNA technology when applied to aggressive B-cell lymphoma.

  Study EGAS50000000968