7088 results for "canc*"

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• Targeted_NanoSeq_Buccal

  Targeted NanoSeq in buccal epithelium obtained longitudinally from a number of donors. A custom-designed panel of ~200 genes will be used to achieve high depth coverage (aiming for ~1000X at panel sites).

  Study EGAS00001005925

• Genome-wide search for higher order epistasis as modifiers of treatment effects on bone mineral density in childhood cancer survivors

  Survivors of pediatric acute lymphoblastic leukemia (ALL) exposed to curative treatments that adversely affect BMD (age- and sex-adjusted BMD Z-scores, measured via QCT). Specifically, after SNP QC and annotation, we considered 75523 autosomal SNPs mapped to putative promoter or enhancer regions to restrict our search to 3-way SNP interactions that potentially reflect gene regulation events that influence BMD. We replicated 3-SNP interactions as modifiers of treatment effects in a cohort of adult survivors of non-ALL pediatric cancers (N=1428).

  Study EGAS00001002645

• ET_Exome

  Agilent whole exome hybridisation capture will be performed on genomic DNA derived from 50 Essential Thrombocythemia Myeloproliferative Disease samples and matched normal DNA from the same patients. Samples will be multiplexed in one lane of Illumina HiSeq. Sequencing to a coverage of at least 30x will be performed and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes.

  Study EGAS00001000102

• Genomic analysis Nasopharyngeal cancer through whole exome sequencing and whole genomic sequencing.

  Nasopharyngeal carcinoma (NPC) is a squamous-cell carcinoma and has remarkable ethnic and geographic distribution, with a high prevalence in southern China, southeast Asia, northern Africa and Alaska. Although there are previous studies implicated NF-κB pathway play an important role in NPC. Newer research also found several important cellular processes and pathways in NPC, including chromatin modification, ERBB-PI3K signaling and autophagy machinery. Put these studies together, although, NPC is still poorly understood at the genetic level. Here we determined the mutational landscape of 553 cases with NPC using whole-genomic and whole-exome sequencing. These approaches revealed a distinct mutational signature and significantly mutated genes.

  Study EGAS00001002788

• Whole genome sequencing with linked reads of pediatric glioblastoma samples

  Pediatric glioblastoma (pGBM) is a lethal cancer with no effective therapies. To understand mechanisms of tumor evolution in this cancer, we performed whole genome sequencing with linked reads on longitudinally resected pGBM samples. Our analyses showed that all diagnostic and recurrent samples were collections of genetically diverse subclones. Clonal composition rapidly evolved at recurrence, with less than 8% of non-synonymous single nucleotide variants being shared in diagnostic-recurrent pairs. In order to track the origins of the mutational events we observed in pGBM, we generated whole genome datasets for two patients and their parents. These trios showed that genetic variants could be (i) somatic, (ii) inherited from a healthy parent, or (iii) arose de novo in the germlines of pGBM patients. Analysis of variant allele frequencies supported a model of tumor growth involving slow-cycling cancer stem cells that give rise to fast-proliferating progenitor-like cells and to non-dividing cells. Interestingly, radiation and anti-mitotic chemotherapeutics did not increase overall tumor burden upon recurrence. These findings support an important role for slow-cycling stem cell populations in contributing to recurrences, since slow-cycling cell populations are expected to be less prone to genotoxic stress induced by these treatments and to accumulate few mutations. Our results highlight the need for new targeted treatments that account for the complex functional hierarchies and genomic heterogeneity of pGBM.

  Study EGAS00001003432

• The_life_history_of_colorectal_cancer_metastases_study_WGS_X10

  Whole genome sequencing of a series of metastasis collected from 2 patients at autopsy will be used to construct a life history of the cancer, including phylogenetic relationship between the different metastases an also whether there is evidence of convergence towards common biological processes that underpin the metastatic process but though different mutational events

  Study EGAS00001000864

• 1__Fanconi_Anemia_transformation_to_AML

  Genomic libraries (500 bps) will be generated from total genomic DNA derived from 7 Fanconi anemia (FA) derived Acute myeloid leukemia samples and subjected to total of two lanes of 50 bp, paired end sequencing on the llumina HiSeq. Paired reads will be mapped to build 37 of the human reference genome to facilitate the generation of genome wide copy number information, and the identification of novel rearranged cancer genes and gene fusions.

  Study EGAS00001000033

• Genome-wide mutational consequences of nucleotide excision repair-deficiency through XPC deletion in a human adult stem cell culture

  Nucleotide excision repair (NER) is one of the main DNA repair pathways that protect cells against genomic damage. Deficiency in this pathway can contribute to the development of cancer and accelerate aging. NER-deficiency is an important determinant for cancer treatment outcome, as NER-deficient tumors are selectively sensitive to cisplatin treatment. While NER-deficiency has been linked to mutational Signature 5, not all NER-deficient tumors are characterized by a high Signature 5 contribution, illustrating the importance to further characterize the mutational consequences of NER-deficiency. Here, we analyzed the mutational profile of a human adult stem cell (organoid) culture that is deficient in NER through XPC deletion by CRISPR-Cas9 gene-editing, and subsequent whole-genome sequencing analysis of a clonally derived organoid. We found that XPC deletion results in an increase in base substitution load and specifically induces Signature 8 mutations, a mutational signature with previously unknown etiology. Presence of Signature 8 may, therefore, serve as a novel biomarker for NER-deficient tumors and could improve personalized treatment strategies.

  Study EGAS00001002681

• Characterization of genetic intratumor heterogeneity in colorectal cancer and matching patient-derived spheroid cultures.

  Patient-derived in vitro cultures of colorectal cancer (CRC) may help guide treatment strategies prior to patient treatment. However, most previous studies have been performed on a single biopsy per tumor. The purpose of this study was to analyze multiple spatially distinct biopsies from CRCs and see how well intratumor heterogeneity (ITH) was recapitulated in matching patient-derived spheroids. Three to five biopsies were collected from six CRC tumors. Each biopsy was split in two; one half was used for spheroid culturing, the other half was used for direct DNA and RNA purification. For two of the patients, lymph node metastases were analyzed. Somatic mutations were called from whole exome sequencing data. Each tumor contained multiple mutations shared across all biopsies and spheroids, including major CRC drivers such as APC, KRAS, and TP53. At the same time, all tumors exhibited ITH on both mutation and copy number level. The concordance between biopsies and spheroids ranged between 40-70% for coding mutations. For three of the patients the biopsy and spheroid from matching areas clustered together, meaning that the spheroid resembled the area of origin more than the other areas. However, all biopsies and spheroids contained private mutations. Thereby, multiple cultures from spatially distinct sites of the tumor increase the insight into the genetic profile of the entire tumor. RNA sequencing based molecular subtyping was stable and seemed independent of genetic ITH. In conclusion, all examined CRC tumors contained genetic ITH on mutation and copy number level. Spheroid cultures partly reflected this ITH, meaning that multiple cultures from distinct sites of the tumor improved the representation of the different genetic subclones in the primary tumor. This should be taken in to account when establishing patient-derived models for drug screening.

  Study EGAS00001002684

• WGS of breast cancer diagnosed during pregnancy and matched control

  The aim of this study was to compare the mutational landscape of breast cancer diagnosed during pregnancy (BCP) and breast cancer from age/stage non-pregnant patients (controls). We present whole genome sequencing data (Illumina HiSeq X ten platform) of tumor and matched normal tissues from 35 BCP patients and 20 controls. This work provides important novel biological insights and a unique resource to study the biology of breast cancer in young women and how pregnancy could modulate tumor biology.

  Study EGAS00001002685