11768 results for "cancer rna-seq"

in 19.38 milliseconds.

• Human brain development single cell sequencing

  379 tissue samples from various parts of the developing human embryo brain were dissociated and single cells were collected and processed without bias for mRNA-seq using 10X chromium 3' protocol. Libraries were sequenced on Illumina NovaSeq and reads aligned against the human GRCh38 genome.

  Dataset EGAD00001006049

• HiC-sequencing in human monocyte differentiation

  This dataset consists of in situ HiC-seq data from human monocytes, monocyte-derived dendritic cells as well as monocyte-derived cells that were subjected to siRNA treatment targeting CTCF or RAD21. In total, the data set includes 42 samples.

  Dataset EGAD00001007955

• AML-PMP miRNA-Seq

  miRNA libraries of the AML-PMP project were sequenced on the Illumina HiSeq 2000 instrument, approximately 16 samples per HiSeq lane, to a median depth of 5.7 million reads per library.

  Dataset EGAD00001009772

• Low-pass whole-genome DNA sequencing of cohesin-mutated and wildtype adult AMLs

  Low-pass whole-genome DNA sequencing of cohesin-mutated (STAG2 or RAD21 mutations) and wildtype (CTRL-AML) adult AMLs generated generated from ultrasound-fragmented genomic DNA. Samples were only sequenced shallow (20-40 Mio reads) Used for digital karyotyping and ChIP-seq background/copy-nuber normalization/correction.

  Dataset EGAD00001011207

• Single nucleus and in situ RNA sequencing reveals cell topographies in the human pancreas

  Molecular evidence of cellular heterogeneity in the human exocrine pancreas has not been established, due to the local concentration of hydrolytic enzymes that can rapidly degrade cells and RNA upon resection. Here we innovated single-nucleus RNA sequencing protocols, and profiled more than 120,000 cells from adult and neonatal human donors to create the first comprehensive atlas of human pancreas cells, including epithelial and non-epithelial constituents. Adult and neonatal pancreata shared common features, including the presence of previously undetected acinar subtypes, but also showed marked differences in the composition of the endocrine, endothelial, and immune compartments. Spatial cartography, including cell proximity mapping through in situ sequencing, revealed dynamic developmental cell topographies in the endocrine and exocrine pancreas. Our human pancreas cell atlas can be interrogated to understand pancreatic cell biology, and provides a crucial reference set for future comparisons with diseased tissue samples to map the cellular foundations of pancreatic diseases.

  Study EGAS00001004653

• RNA sequencing data for primary and recurrent ovarian granulosa cell tumors

  RNA sequencing dataset for primary and recurrent ovarian granulosa cell tumors consists of 24 .bam files with aligned reads, including 8 primary and 16 recurrent tumors. Total RNA was extracted from cryopreserved tissue of adult-type granulosa cell tumor samples. Libraries were prepared from cDNA using the NuGEN Ovation Ultralow Library System V2 (San Carlos, CA). Paired-end bulk RNA sequencing was performed on the Illumina HiSeq 2000 platform. RNA sequencing reads were aligned to the hg19/GRCh37 reference human genome using the STAR software (version 2.6.0b) with default parameters. Samples description: GCT001 Adult-type Granulosa Cell Tumor: recurrent tumor GCT002 Adult-type Granulosa Cell Tumor: primary tumor GCT003 Adult-type Granulosa Cell Tumor: recurrent tumor GCT004 Adult-type Granulosa Cell Tumor: primary tumor GCT005 Adult-type Granulosa Cell Tumor: recurrent tumor GCT006 Adult-type Granulosa Cell Tumor: recurrent tumor GCT007 Adult-type Granulosa Cell Tumor: primary tumor GCT008 Adult-type Granulosa Cell Tumor: recurrent tumor GCT009 Adult-type Granulosa Cell Tumor: recurrent tumor GCT010 Adult-type Granulosa Cell Tumor: recurrent tumor GCT011 Adult-type Granulosa Cell Tumor: primary tumor GCT012 Adult-type Granulosa Cell Tumor: recurrent tumor GCT013 Adult-type Granulosa Cell Tumor: recurrent tumor GCT014 Adult-type Granulosa Cell Tumor: recurrent tumor GCT015 Adult-type Granulosa Cell Tumor: recurrent tumor GCT016 Adult-type Granulosa Cell Tumor: recurrent tumor GCT017 Adult-type Granulosa Cell Tumor: recurrent tumor GCT018 Adult-type Granulosa Cell Tumor: primary tumor GCT019 Adult-type Granulosa Cell Tumor: recurrent tumor GCT020 Adult-type Granulosa Cell Tumor: primary tumor GCT021 Adult-type Granulosa Cell Tumor: primary tumor GCT022 Adult-type Granulosa Cell Tumor: recurrent tumor GCT023 Adult-type Granulosa Cell Tumor: recurrent tumor GCT024 Adult-type Granulosa Cell Tumor: primary tumor

  Dataset EGAD00001009108

• LINE_luminal_breast_cancer_Neoadjuvant_Chemotherapy_Study

  A targeted gene screen of 365 known cancer genes in luminal breast cancer samples pre-chemotherapy and at resection post-chemotherapy to evalaute clonal expansion of chemotherapy cancer cells.

  Study EGAS00001001223

• prDLBCL WXS/RNA Data Commitee

  Dac EGAC50000000284

• Longitudinal Multi-Omic Immune Resource Reveals Dynamic Responses in Healthy Human Aging

  The generation and maintenance of protective immunity is a dynamic interplay between host and environment that is impacted by age. Understanding fundamental changes in the healthy immune system that occur over a lifespan is critical in developing interventions for age-related susceptibility to infections and diseases. Here, we use multi-omic profiling (scRNA-seq, proteomics, flow cytometry) to examine human peripheral immunity in over 300 healthy adults, with 96 young and older adults followed over two years with yearly vaccination. The resulting resource includes scRNA-seq datasets of >16 million PBMCs, interrogating 71 immune cell subsets from our new Immune Health Atlas. This study allows unique insights into the composition and transcriptional state of immune cells at homeostasis, with vaccine perturbation, under Cytomegalovirus (CMV) infection and across age. We find that T cells specifically accumulate age-related transcriptional changes more than other immune cells, independent from inflammation and chronic perturbation. Moreover, impaired memory B cell responses to vaccination are linked to a Th2-like state shift in older adults' memory CD4 T cells, revealing possible mechanisms of immune dysregulation during healthy human aging. This extensive resource is provided with a suite of exploration tools at https://apps.allenimmunology.org/aifi/insights/dynamics-imm-health-age/ to enhance data accessibility and further the understanding of immune health across age. Please note that the Sound Life Cohort raw data are spread across three dbGap submissions: phs003841.v1 (this study), phs003944.v1, and phs003400.v1.

  Study phs003841

• Bulk RNAseq of cultured fibroblasts

  Fastq files from bulk RNAseq of fibroblasts after culture and facs sorting (N=9). Sorted FAP+ CAF cells RNAs were extracted using Qiagen miRNeasy Kit (Qiagen, #217004) according to the manufacturer's instructions. Verification of RNA integrity and quality was performed using the Agilent RNA 6000 nano Kit (Agilent Technologies, #5067-1511). cDNA libraries were prepared using the TruSeq Stranded mRNA Kit (Illumina, #20020594) followed by sequencing on NovaSeq (Illumina).

  Dataset EGAD50000000323

• RNAseq of preneoplasia lung adenocarcinoma

  RNA sequencing of 168 pulmonary samples including lung preneoplasia atypical adenomatous hyperplasia (AAH, N=38), adenocarcinoma in situ (AIS, N=22), minimally invasive adenocarcinoma (MIA, N=19) and invasive lung adenocarcinoma (ADC, N=38) and adjacent lung tissues (Normal, N=62).

  Study EGAS50000000271

• Blood Handling and Leukocyte Isolation Methods Impact the Global Transcriptome of Immune Cells

  In order to characterize the effects of upstream sample handling on the transcriptome of isolated leukocyte populations, we simulated various sample handling methods on whole blood prior to leukocyte isolation for low-input RNA-sequencing.

  Study phs001563

• The Normal Human Tissue Sequencing Project: Non-Diseased, Non-Malignant Tissues

  The Normal Human Tissue Sequencing Project provides RNA expression and DNA methylation data from normal (non-diseased) human tissues. This data set from a variety of source tissue is a valuable resource for human disease studies.

  Study phs000819

• Dataset for WGS and RNA samples of acute myeloid leukemia with MNX1 expression (non-hipo)

  This dataset contains 115 samples of WGS, ATAC, 4C and RNAseq samples of patients with acute myeloid leukemia. The sequencing was performed on Illumina HiSeq 4000, 2000 and HiSeq X using Illumina TruSeq Nano DNA and Agilent Strand Specific RNA Kits. The sequencing was always paired.

  Dataset EGAD50000001097

• Single cell RNA sequencing of co-culture of human organoids with polarized pro-inflammatory (M1) or anti-inflammatory (M2) macrophages

  In order to know if the mechanisms we identified in mice – demonstrating that macrophages are able to orchestrate the intestinal regenerative process – are conserved in humans we develop a co-culture system with human intestinal organoids and human polarized macrophages. We co-culture human organoids with pro-inflammatory or anti-inflammatory macrophages for 48h. On day 3 cells were collected to perform single cell RNA sequencing.

  Dac EGAC50000000270

• Whole-transcriptome sequencing of tumor samples

  Whole transcriptome sequencing of RNA samples from tumor samples of patients in the Neo-Pembro trial. For each patient, up to three samples were sequenced; one tumor biopsy at baseline, one tumor biopsy after induction chemotherapy, and a tumor sample from resection material at cytoreductive surgery. RNA was obtained from fresh-frozen samples where possible, or formalin-fixed paraffin-embedded when no fresh-frozen sample was available.

  Dataset EGAD50000001151

• Effects of KSP inhibitor filanesib in aggressive hepatoblastoma PDX cells

  Aim of this RNA sequencing dataset has been to asses effects caused by the KSP inhibitor filanesib in aggressive hepatoblastoma PDX cells. Two cell lines (HB-279 and HB-284) were utilised. DMSO-treated cells were used as controls.

  Study EGAS50000000899

• Comparison clinical recommendation MASTER and panel sequencing: RNA data

  This dataset contains 19 case/control samples of RNA sequencing data. Sequencing was performed on Illumina HiSeq 4000 and NovaSeq 6000 using TruSeq Stranded mRNA Kit. The sequencing was always paired.

  Dataset EGAD50000000625

• RNAseq

  Libraries for sixty-eight cases (23 EATL and 45 MEITL) were prepared starting from 1 µg of total RNA using the TruSeq Stranded total RNA Gold kit from Illumina (San Diego, California, USA) and were sequenced in three batches on a HiSeq 4000 machine from Illumina with an average output of 63 million reads per sample (range 49-126).

  Dataset EGAD50000001619

• B cells (CD19) RNAseq dataset of JIA patients with known uveitis status.

  CLUSTER consortium RNA sequencing dataset from UK JIA patient cohort with documented uveitis status. Peripheral blood mononuclear cells (PBMCs) were isolated from blood samples and cryopreserved. Samples were subsequently thawed and flow-sorted for CD19+ B cells prior to RNA sequencing. Clinical metadata includes patient demographics and uveitis status at time of sampling.

  Dataset EGAD50000001616

• RNAseq of human intestinal epithelial cell layers cultured in OGM, ENR, and ENRRT

  This dataset contains RNA sequencing data in fastq and bam format from 24 samples of human jejunum organoids grown in 3D configuration or as 2D monolayers on anodisc imaging chambers (AICs) in medium formulations OGM, ENR, and ENRRT. The RNA sequencing samples were sequenced using paired-end sequencing (2x150 bp) on an Illumina NovaSeq 6000 instrument at the SciLifeLab National Genomics Infrastructure (NGI) in Uppsala.

  Dataset EGAD50000001766

• Comprehensive molecular and clinicopathological profiling of desmoid tumors

  Previous studies have not clearly identified a prognostic factor for desmoid tumors (DT). Whole-exome sequencing and/or RNA sequencing were performed in 64 cases of DT to investigate the molecular profiles in combination with the clinicopathological characteristics.

  Study JGAS000270

• Genome-wide integrative analysis of pediatric pancreatoblastoma

  Pancreatoblastoma is the most common pancreatic malignancy of young children, but its molecular pathogenesis remains poorly understood. To understand the molecular pathogenesis of pancreatoblastoma, we comprehensively analysed the whole exome sequencing, RNA sequencing, SNP array, and methylation array data of pancreatoblastoma.

  Study JGAS000088

• Integrated genetic and epigenetic analysis of myxofibrosarcoma

  Myxofibrosarcoma (MFS) is a common histological subtype of adult soft tissue sarcoma characterized by an infiltrative growth pattern and a high propensity for local recurrence. We underwent whole exome sequencing, RNA sequencing, and methylation analysis of MFS.

  Study EGAS00001002889

• Gene_epression_regulation_in_cytokine_induced_immune_cell_states

  We isolated T cells and monocotyes from healthy platelet donors and cultured them in resting and stimulated conditions with addition of a range of cytokines. We performed RNA sequencing to assess impact of different disease-relevant cytokines upon immune cell responses.

  Study EGAS00001003823

• Potent neutralizing antibodies against SARS-CoV-2

  The COVID-19 pandemic urgently needs therapeutic and prophylactic interventions. Here we report the rapid identification of SARS-CoV-2 neutralizing antibodies by high-throughput single-cell RNA and VDJ sequencing of antigen-enriched B cells from 60 convalescent patients.

  Study EGAS00001004412

• HLF COPD Transcriptomics

  We generated transcriptomes of primary human lung fibroblasts (HLFs) isolated from distal parenchyma of ex-smoker controls and COPD patients, with both mild and severe disease. RNA sequencing analysis demonstrated dysregulation of genes involved in proliferation, DNA repair, and extracellular matrix organization.

  Study EGAS00001006602

• Transcriptomic analysis of MYC overexpression in LT-HSC.

  Long-term hematopoietic stem cells (LT-HSC) were sorted from human cord blood and cultured overnight before transduction with lentiviral vectors (empty E CTRL or MYC). Six days after transduction, BFP+ transduced cells were sorted for RNA extraction and sequencing

  Study EGAS00001004970

• Isoform-level profiling of m6A modifications in human brain

  Oxford Nanopore direct RNA sequencing (DRS) can quantify isoform expression, modifications and polyA tail lengths, enabling simultaneous investigation of the transcriptome and epitranscriptome. We applied DRS to three post-mortem human brain regions: prefrontal cortex, caudate nucleus and cerebellum.

  Study EGAS00001007742

• Human Biofluid RNA Atlas

  This dataset contains small RNA sequencing data and mRNA capture sequencing data from 20 different human biofluids (amniotic fluid, aqueous humor, ascites, bile, bronchial lavage fluid, breast milk, cerebrospinal fluid, colostrum, gastric fluid, pancreatic cyst fluid, plasma, saliva, seminal fluid, serum, sputum, stool, synovial fluid, sweat, tear fluid and urine). In total, 180 samples were sequenced. Files are provided in fastQ format. Samples were sequenced on a NextSeq 500.

  Dataset EGAD00001005439

• TSGKO_RNASeq

  Libraries were prepared from RNA-extracted cell lines using Illumina RNA library prep kit. Samples were sequenced on Illumina HiSeq 4000 or HiSeq 2500.

  Dataset EGAD00001008559

• Circular RNA characterization in functionally distinct brain regions

  RNA extracted from middle temporal gyrus (MG) brain region of healthy elderly controls. Three pairs of samples were generated, each pair consisting of one sample that was enriched for circular RNAs using RNase R, and a second sample that was not enriched (total N=6). Remaining samples in the study from other functionally distinct brain regions are currently under process and will be released soon.

  Dataset EGAD00001004211

• RNAseq_pituitary_adenoma

  Total RNA was extracted using RNAble (Eurobio), cleaned-up with RNeasy columns (Qiagen) and sequenced. The libraries were prepared at the Genomics Platform of the Cochin Institute, following the TruSeq Stranded mRNA protocol (Illumina), starting from 1 µg of high quality total RNA. Paired end (2 × 75 bp) sequencing was performed on a Nextseq 500 platform (Illumina). FASTQ sequences were aligned on hg19 (GRCh37) human reference genome with STAR (v.2.5.2a)

  Dataset EGAD00001004996

• RNA-sequencing of six Pilocytic astrocytoma tumors

  Total stranded TruSeq RNA sequencing by Illumina of six tumor samples from six cases of pediatric Pilocytic astrocytoma. The data is published in the following paper: Tomic TT, Olausson J, Wilzen A, Sabel M, Truve K, Sjogren H, Dosa S, Tisell M, Lannering B, Enlund F, Martinsson T, Aman P, Abel F. A new GTF2I-BRAF fusion mediating MAPK pathway activation in pilocytic astrocytoma. PLoS One. 2017 Apr 27;12(4):e0175638.

  Dataset EGAD00001003143

• Peripheral blood RNA-sequencing in 4,732 participants of the INTERVAL cohort

  We performed bulk RNA-sequencing on peripheral blood collected from 4,732 blood donors recruited as part of the INTERVAL study. Using these data, we mapped gene expression and splicing quantitative trait loci (QTLs). Then, we integrated these data with protein, metabolite and lipid QTLs in the same individuals. The study aimed to identify the shared genetic etiology across transcriptional phenotypes, molecular traits and health outcomes in humans.

  Dataset EGAD00001008015

• oncogenic gene fusions in primary colon cancers

  This dataset represents RNA-sequencing data from 278 primary colon cancers obtained from fresh-frozen tumor sections. RNA-sequencing was performed using TruSeq library preparation and samples were sequenced on Illumina NextSeq and HiSeq. The data are available as Illumina NextSeq and HiSeq fastq files (_R1.fastq and _R2.fastq for each tumor sample, 556 files in total).

  Dataset EGAD00001003291

• RNA-sequencing data from human FSHD and control skeletal muscle biopsies

  This project includes RNA-sequencing data from human FSHD and control skeletal muscle biopsies. This project includes data from 28 FSHD patients (total 37 samples, including vastus lateralis and tibialis anterior muscles) and 12 control individuals (total 24 samples, including vastus lateralis and tibialis anterior muscles).

  Dataset EGAD00001008337

• Exome and RNA-sequencing data from a relapsed t(1;19) acute lymphoblastic leukemia

  Sequence data is from 4 samples from an adult patient with TCF3-PBX1 t(1;19)-positive acute lymphoblastic leukemia. Exome sequencing was performed on a skin biopsy (normal tissue control) and leukemic bone marrow biopsies taken at diagnosis and at two relapse time points. RNA-sequence data is from leukemic bone marrow from two relapse biopsies.

  Dataset EGAD00001002203

• RNA sequencing of cytokine-induced T cell responses

  Cytokines affect T cell responses by polarising them to different phenotypes. We isolated T cells from healthy platelet donors and cultured them in resting and stimulated conditions, as well as in the presence of Th1, Th2, Th17 and iTreg cocktail. In addition, T cells were stimulated in the presence of IL-10, IL-21, IL-27, IFNb and TNFa. We performed bulk RNA sequencing to assess impact of different disease-relevant cytokines upon T cell response.

  Dataset EGAD00001005291

• RNA-sequencing and targeted DNA-sequecing of human thyroid tumors and normal samples

  RNA-sequencing data: 5 normal thyroid tissues, 14 papillary thyroid carcinomas, 2 lymph node metastases, 19 poorly differentiated thyroid carcinomas and 17 anaplastic thyroid carcinomas; Targeted DNA-sequencing of the 165 genes included in the “Solid and Haematological tumors” panel (BRIGHTCore, Brussels, Belgium): 2 normal thyroid tissues, 2 poorly differentiated thyroid carcinomas and 7 anaplastic thyroid carcinomas; 2 FASTQ files for each sample (paired).

  Dataset EGAD00001011678

• Improved Sezary cell detection and novel insights into immunophenotypic and molecular heterogeneity in Sézary syndrome

  We performed a prospective investigation in Sézary syndrome by the application of a standardized multiparameter flow cytometry, FACS-cell sorting, and RNA-sequencing for an in-depth immunophenotypic and transcriptional profiling of Sézary cells.

  Study EGAS00001005229

• Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) - Genome-Wide Association Study Meta-Analysis

  Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) was one of five projects funded in 2010 as part of the NCI's Genetic Associations and Mechanisms in Oncology (GAME-ON) initiative (http://epi.grants.cancer.gov/gameon/). GAME-ON's overall goal was to foster an intra-disciplinary and collaborative approach to the translation of promising research leads deriving from the initial wave of cancer GWAS. Specific goals included replication of previous GWAS findings and identification of new susceptibility loci through meta analyses of existing GWAS data and fine mapping of identified loci to better pinpoint causal variants; and identify germline variants that are associated with risk of multiple cancers. The other four funded GAME-ON projects were: the ColoRectal TransdisciplinaryStudy (CORECT), Elucidating Loci Involved in Prostate Cancer Susceptibility (ELLIPSE), Follow-up of Ovarian Cancer Genetic Association and Interaction Study (FOCI), and Transdisciplinary Research in Cancer of the Lung (TRICL). To identify additional cancer risk loci, improve the precision of fine-mapping, and facilitate cross-cancer analyses, DRIVE investigators performed a meta-analysis of eleven genome-wide association studies of breast cancer: The Australian Breast Cancer Family Study (ABCFS), the British Breast Cancer Study (BBCS), the Breast and Prostate Cancer Cohort Consortium (BPC3), the Breast Cancer Family Registries (BCFR), the Dutch Familial Bilateral Breast Cancer Study (DFBBCS), German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC), the Helsinki breast cancer family Study (HEBCS), the Mammary Carcinoma Risk factor Investigation (MARIE), the Singapore and Sweden Breast Cancer Study (SASBAC), the Triple Negative Breast Cancer Study (TNBC), and the UK2 GWAS. These studies comprised a total of 16,062 cases and 46,157 controls. Imputation to the 1,000 Genomes Project Phase 1 v3 ALL reference panel was performed by study, and summary statistics from each study were combined using fixed-effect meta analysis.

  Study phs001263

• DAC for "Longitudinal copy number variation analysis from plasma DNA of head and neck cancer patients under re-radiotherapy"

  This is the DAC for "Longitudinal copy number variation analysis from plasma DNA of head and neck cancer patients under re-radiotherapy" with Florian Janke f.janke@dkfz-heidelberg.de German Cancer Research Center, Division of Cancer Genome Research Holger Sültmann h.sueltmann@dkfz-heidelberg.de German Cancer Research Center, Division of Cancer Genome Research Magdalena Görtz magdalena.goertz@dkfz-heidelberg.de German Cancer Research Center, Multiparametric Methods for Early Detection of Prostate Cancer

  Dac EGAC50000000114

• Dataset for hepatopancreaticobiliary_malignancy-RNA

  Rare cancer sequencing data of 119 runs in tumor/control pairs, which were uploaded to umbrella studies. The sequencing was always paired

  Dataset EGAD00001008863

• Custom long non-coding RNA capture DAC

  Dac EGAC00001002198

• GLASS-NL RNA-sequencing Study

  Study EGAS00001007551

• Detection and characterization of lung cancer using cell-free DNA fragmentomes

  Lung cancer remains the leading cause of cancer death world-wide, largely due to its late diagnosis. Non-invasive approaches for assessment of cell-free DNA (cfDNA) provide an opportunity for detection and intervention that may have broader accessibility than current imaging approaches. Using a machine learning model for detecting tumor-derived cfDNA through genome-wide analyses of cfDNA fragmentation, we examined a prospective study of 365 individuals at risk for lung cancer (Lung Cancer Diagnostic Study, LUCAS), including 129 individuals ultimately diagnosed with lung cancer and 236 individuals determined to not have lung cancer. We externally validated the cancer detection model using an independent cohort of 385 non-cancer individuals and 46 predominantly early stage lung cancer patients. Combining fragmentation features with clinical risk factors and CEA levels followed by CT imaging detected 94% of patients with cancer across stages and subtypes, including 91% of stage I/II and 96% of stage III/IV, at 80% specificity. Genome-wide fragmentation profiles across ~13,000 ASCL1 transcription factor binding sites could be used to distinguish individuals with small cell lung cancer (SCLC) from those with non-small cell lung cancer (NSCLC) with high accuracy (AUC=0.98). Among individuals with lung cancer, a higher cfDNA fragmentation score was associated with tumor size and invasion, and represented an independent prognostic indicator of survival. These studies provide a facile approach for non-invasive detection of lung cancer and clinical management of this disease.

  Study EGAS00001005340

• ATAC-seq: Acquired non-permissive bone marrow microenvironment impairs hematopoietic stem cell proliferation and maintenance and B-cell development post-HSCT

  Defects in B-cell reconstitution upon hematopoietic stem-cell (HSC) transplantation (HSCT) are a common observation, yet the mechanism remains unexplained. The bone marrow (BM) stroma, including mesenchymal stromal cells (MSCs), guides HSC maintenance and B-lymphopoiesis by secreting crucial cytokines. We report acquired, permanent, selective and complete B-cell deficiency in the context of full donor-chimerism in a patient with X-linked lymphoproliferative disease and aimed to identify the contribution of the BM-microenvironment in disrupted B-cell reconstitution post-HSCT. We studied longitudinal BM samples from the patient and his identical twin, both of whom underwent HSCT with the same donor with opposite outcomes in B-cell reconstitution. In the index patient BM, we observed progressive loss of proliferation of HSCs and a selective block at the pre-BI cell stage. In vitro modeling studies showed limited survival of patient-HSCs and a relative accumulation of pre-B cells. Patient-derived MSCs failed to support survival and proliferation of HSCs and B-cell development of healthy-HSCs which was correlated with reduced CXCL12 levels. Using bulk RNA-sequencing of MSCs and in vitro functional studies, we showed global changes in the patients’ MSCs and a progressive loss of CXCL12 expression. Indeed, survival of patients HSCs improved supplementing in vitro development culture with CXCL12, suggesting a contribution of defective CXCL12 signaling to the phenotype. In summary, our data show that an acquired defect in the BM-stromal microenvironment and exhaustion of HSCs and committed progenitors may cause a permanent non-permissive state for normal B-cell development.

  Study EGAS50000001438

• Cancer Risk Estimates Related to Susceptibility Genes (CARRIERS)

  The CARRIERS study utilized custom amplicon-based variant screening of known cancer predisposition genes in germline DNA from breast cancer cases and age matched unaffected controls taken from predominantly cohort-based breast cancer case-control studies to establish the risks of breast cancer associated with pathogenic variants in these genes.

  Study phs002820

• Identification of Targetable FGFR Gene Fusions in Diverse Cancers

  In this study, patients with advanced cancer across all histologies were enrolled in our IRB approved clinical sequencing program, called MI-ONCOSEQ, to go through an integrative sequencing which includes whole exome sequencing of the tumor and matched normal, and transcriptome sequencing. Four index cases were identified which harbor gene rearrangements of FGFR2 including two cholangiocarcinoma cases, a metastatic breast cancer case, and a metastatic prostate cancer case. After extending our assessment of FGFR rearrangements across multiple tumor cohorts, including TCGA, we identified FGFR gene fusions with intact kinase domains of FGFR1, FGFR2, or FGFR3 in cholangiocarcinoma, breast cancer, prostate cancer, lung squamous cell cancer, bladder cancer, thyroid cancer, oral cancer, glioblastoma, and head and neck squamous cell cancer. All FGFR fusion partners tested exhibit oligomerization capability, suggesting a shared mode of kinase activation. Overexpression of FGFR fusion proteins in vitro induced cell proliferation, and bladder cancer cell lines that harbors FGFR3 fusion proteins exhibited enhanced susceptibility to pharmacologic inhibition in vitro and in vivo. Due to the combinatorial possibilities of FGFR family fusion to a variety of oligomerization partners, clinical sequencing efforts which incorporate transcriptome analysis for gene fusions are poised to identify rare, targetable FGFR fusions across diverse cancer types.

  Study phs000602