12219 results for "cancer rna-seq"

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• Genomic Resistance Patterns to Second Generation Androgen Blockade in Paired Tumor Biopsies of Metastatic Castrate-Resistant Prostate Cancer

  We examined genetic resistance to second generation androgen targeting therapies (abiraterone acetate or enzalutamide) by analyzing whole exome sequencing of patient-matched pre-treatment and post-resistance tumors from a series of castrate-resistant prostate cancer (CRPC) patients. Abiraterone resistant tumors harbored alterations in AR and MYC, whereas patients treated with enzalutamide had acquired alterations in the cell cycle pathway. We experimentally confirmed expression of cell-cycle kinases sufficed to drive enzalutamide resistance, which was mitigated through CDK4/6 blockade. These observations link genetic resistance to specific therapeutic agents to inform strategies in genomically selected advanced CRPC.

  Study phs001447

• Radiation-Related Genomic Profile of Papillary Thyroid Cancer after the Chernobyl Accident

  The April 26, 1986 accident at the Chernobyl nuclear power plant in northern Ukraine resulted in the release of radioactive contaminants, which were deposited in the surrounding areas in Ukraine, Belarus, and Russia. The main radiation-related health effect resulting from these exposures is the increased occurrence of thyroid cancer among individuals who were children at the time of the accident or born shortly thereafter. The purpose of this study was to conduct a comprehensive genomic landscape analysis of papillary thyroid tumors arising in individuals who were exposed as children to radioactive iodine (I-131) from the Chernobyl nuclear power plant accident.

  Study phs001134

• scRNAseq analysis of CD8 T cells infiltrating the bladder and tumor of 4 non-muscle-invasive bladder cancer patients, before and after BCG treatment.

  We performed scRNAseq analysis of CD8 T cells infiltrating the bladder and tumor of 4 non-muscle-invasive bladder cancer patients, before and after BCG treatment. In order to identify tumor-specific T cells, we selected CD8 T cells that were enriched in the tumor of the patient. We also selected CD8 T cells appearing in the bladder after BCG treatment, with the hypothesis that BCG treatment stimulates tumor-specific CD8 T cells. Next, we cloned the TCR of these T cells in a Jurkat cell line and tested these TCR for recognition of tumor-specific antigens.

  Study EGAS50000001384

• Identification of cis-regulatory mutations generating de novo edges in personalized cancer gene regulatory networks

  The identification of functional non-coding mutations is a key challenge in the field of genomics. Here we introduce μ-cisTarget to filter, annotate and prioritize cis-regulatory mutations based on their putative effect on the underlying ‘personal’ gene regulatory network. We validated μ-cisTarget by re-analyzing the TAL1 and LMO1 enhancer mutations in T-ALL, and the TERT promoter mutation in melanoma. Next, we re-sequenced the full genome of ten cancer cell lines and used matched transcriptome data and motif discovery to identify master regulators with de novo binding sites that result in the up-regulation of nearby oncogenic drivers.

  Study EGAS00001002571

• Rapid response of APC/TP53/KRAS mutated stage IV colorectal cancer under FOLFIRI + Bevacizumab detected by liquid biopsy: a case report

  In our non-interventional liquid biopsy study, a male patient in his fifties diagnosed with stage IV colorectal cancer and polytope liver metastases rapidly progressed after completing chemotherapy and deceased 8 months after diagnosis. Retrospective cell free DNA testing showed that the APC/TP53/KRAS major clone responded quickly after 3 cycles of FOLFIRI + Bevacizumab. Retrospective exome sequencing of pre-chemotherapy and post-chemotherapy tissue samples including metastases confirmed that the APC/TP53/KRAS and other major clonal mutations (GPR50, SLC5A, ZIC3, SF3A1 and others) were present in all samples. After the last chemotherapy cycle,

  Study EGAS00001004088

• Use_of_Deep_Sequencing_to_Dectect_Clonal_Mutations_In_Sun_Exposed_Skin_Epidermis

  This study aims to define the landscape of somatic mutations in sun exposed human skin by deep sequencing, analyse their frequency and use the data to infer the effect of mutations on proliferating cell behaviour. The frequency of each mutation will reflect the size of the clone of cells in the tissue sample. By analyzing small samples, clones with as few as 100 cells will be detectable. Allele frequency distributions for each mutation will be used to infer cell fate using published methods (Klein et al. 2010). This study will shed unprecedented light on the early clonal events that lead to the emergence of cancer.

  Study EGAS00001000515

• Use_of_Deep_Sequencing_to_Dectect_Clonal_Mutations_In_Sun_Exposed_Skin_Epidermis_PART2

  This study aims to define the landscape of somatic mutations in sun exposed human skin by deep sequencing, analyse their frequency and use the data to infer the effect of mutations on proliferating cell behaviour. The frequency of each mutation will reflect the size of the clone of cells in the tissue sample. By analyzing small samples, clones with as few as 100 cells will be detectable. Allele frequency distributions for each mutation will be used to infer cell fate using published methods (Klein et al. 2010). This study will shed unprecedented light on the early clonal events that lead to the emergence of cancer.

  Study EGAS00001000603

• Inter and intra - tumor heterogeneity in Colorectal Cancer

  We used high depth massive parallel sequencing analyses to study 27 CRC (colorectal cancer) patients, with a total of 97 tumors (both primary and matched metastases) in addition to healthy control samples. We found inter-tumor concordance for coding mutations; in contrast, gene copy numbers were found to be highly discordant between primary tumors and metastases as validated by fluorescent in-situ hybridization. in a further step, we dissected a single tumor into 68 spatially defined samples and sequenced them separately. Here we identify evenly distributed coding mutations in APC and TP53 in all tumor areas, yet highly variable gene copy numbers in numerous genes.

  Study EGAS00001002150

• Combination Therapies for Personalised Cancer Medicine in 11-18

  This study involves mutagenizing 11-18 with ENU to identify those mutations which engender resistance to targeted treatment. In the last decade we have begun to move towards the use of targeted therapeutics in the clinic, often resulting in dramatic response rates in cancer patients. However, clinical experience has demonstrated time and time again that such responses are invariably followed by the development of drug resistance. Identification of the underlying mechanisms may enable us to reverse such resistance. Traditional methods of modelling this resistance in vitro can lead to a plethora of potential resistance mechanisms that can be difficult to decipher.

  Study EGAS00001002579

• Exome array analysis of adverse reactions to fluoropyrimidine-based therapy for gastrointestinal cancer

  Fluoropyrimidines, including 5-fluororacil (5FU) and its pro-drug Capecitabine, are the common treatment for colorectal, breast, neck and head cancers – either as monotherapy or in combination therapy. Adverse reactions (ADRs) to the treatment are common and often result in treatment discontinuation or dose reduction. Factors contributing to ADRs, including genetic variation, are poorly characterized. We performed exome array analysis to identify genetic variants that contribute to adverse reactions.Our final dataset consisted of 504 European ancestry individuals undergoing fluoropyrimidine-based therapy for gastrointestinal cancer. A subset of 254 of these were treated with Capecitabine. All individuals were genotyped on the Illumina HumanExome Array.

  Study EGAS00001002763

• plasma DNA LINE-1 targeted bisulfite sequencing: a new non-invasive multi-cancer detection marker

  The detection of circulating tumor DNA, which allows non-invasive tumor molecular profiling and disease follow-up, promises optimal and individualized management of patients with cancer. However, detecting small fractions of tumor DNA released when the tumor burden is reduced remains a challenge. We developed a PCR-based targeted bisulfite method coupled to deep sequencing to detect methylation patterns of L1PA elements,which we named DIAMOND (for Detection of Long Interspersed Nuclear Element Altered Methylation ON plasma DNA). We used sodium bisulfite chemical conversion to achieve base-pair resolution analysis and designed a multiplexed PCR based on 8 amplicons covering L1PAs .

  Study EGAS50000000446

• Sensitive urothelial cancer detection via high volume urine DNA analysis

  Cystoscopy and imaging are the gold standard for urothelial cancer (UC) detection and surveillance, but cystoscopy is an uncomfortable procedure associated with adverse effects and a low diagnostic yield as only 10% of hematuria patients have UC. Urine tumor DNA (utDNA) is a non-invasive UC biomarker that has suffered from poor sensitivity for Ta stage tumors (<80%). We hypothesized that high urine volume analysis with a multi-gene panel could overcome these limitations, and developed a 100 mL utDNA laboratory platform (UroScout) that analyzes 25 commonly mutated UC genes and 8 copy number-altered loci for somatic alterations to detect UC.

  Study EGAS50000000630

• MutWP5__CRUK_Mutographs_of_Cancer__Lung__PD38234__Targeted_

  Sequencing of LCM-derived microbiopsies from explanted lung from pulmonary fibrosis patient. Goal to assess the mutational burden, spectrum, and clonal dynamics within the tissue. Deep sampling throughout multiple regions of the lung will determine whether there are differences in smoking-related mutation burden in different portions of the lung. Targeted sequencing will be conducted on samples to identify drivers of interest and clonality of the samples, well-performing samples will be sent for subsequent whole-genome sequencing. Results from this portion of the study will be compared to other individuals with smoking-related diseases (COPD, pulmonary fibrosis, lung cancer), and normal, non-smoking lungs.

  Study EGAS00001003325

• Mutational signatures in head and neck cancer (H019)

  Genomic alterations are a driving force in the multistep process of head and neck cancer (HNC) and result from the interaction of exogenous environmental exposures and endogenous cellular processes. Each of these processes leaves a characteristic pattern of mutations on the tumor genome providing the unique opportunity to decipher specific signatures of mutational processes operative during HNC pathogenesis and to address their prognostic value. Computational analysis of whole exome sequencing data of the HIPO-HNC (n=83) and TCGA-HNSC (n=506) cohorts revealed five common mutational signatures (COSMIC signature 1, 2, 3, 13 and 16), and demonstrated their significant association with etiological risk factors (tobacco, alcohol and HPV16).

  Study EGAS00001004588

• Novel driver variants in the histone 3.3 genes, H3F3A and H3F3B, define bone and cartilage cancer sub-types

  A selection of human cancers harbours somatic driver mutations in genes encoding histones, most notably childhood brain tumours with K27M substitutions of the histone 3.3 gene, H3F3A. We performed whole genome sequencing of the benign cartilage tumour, chondroblastoma, and targeted sequencing of histone 3.3 genes, H3F3A and H3F3B, in seven further skeletal tumour types. We identified an exceptionally high prevalence of novel histone 3.3 driver mutations at glycine 34 and at lysine 36. Histone 3.3 gene mutations were found in 91% in giant cell tumours of bone (48/53), mainly H3F3A G34W variants, and in 92% of chondroblastoma (73/79), predominantly K36M mutations in H3F3B. H3F3B is paralogous to the cancer gene H3F3A. However, H3F3B driver variants have not previously been reported in human cancer. Our observation demonstrate remarkable tumour-specificity of mutations, with respect to which histone 3.3 gene and residue is mutated, indicating that the advantage these mutations confer is tumour dependent. Moreover, tumour-specific mutation of H3F3A and H3F3B suggests, that although both genes encode identical proteins, they are likely non-redundant and employed differentially during skeletal development.

  Dataset EGAD00001000646

• Structural rearrangements generate cell-specific, gene-independent CRISPR-Cas9 loss of fitness effects.

  CRISPR-Cas9 genome editing is widely used to study gene function, from basic biology to biomedical research. Structural rearrangements are a ubiquitous feature of cancer cells and their impact on the functional consequences of CRISPR-Cas9 gene-editing has not yet been assessed. Utilizing CRISPR-Cas9 knockout screens for 250 cancer cell lines, we demonstrate that targeting structurally rearranged regions, in particular tandem or interspersed amplifications, is highly detrimental to cellular fitness in a gene independent manner. In contrast, amplifications caused by whole chromosomal duplications have little to no impact on fitness. This effect is cell line specific and dependent on the ploidy status. We devise a copy-number ratio metric that substantially improves the detection of gene-independent cell fitness effects in CRISPR-Cas9 screens. Furthermore, we develop a computational tool, called Crispy, to account for these effects on a single sample basis and provide corrected gene fitness effects. Our analysis demonstrates the importance of structural rearrangements in mediating the effect of CRISPR-Cas9-induced DNA damage, with implications for the use of CRISPR-Cas9 gene-editing in cancer cells.

  Dataset EGAD00001004124

• BAM files of targeted next-generation DNA sequencing data of 13 chordoid gliomas of the third ventricle

  BAM files of targeted next-generation DNA sequencing data of 13 chordoid gliomas of the third ventricle (2 paired tumor-normal samples and 11 tumor-only samples). Genomic DNA was extracted from formalin-fixed, paraffin-embedded blocks of tumor tissue from 13 patients with chordoid glioma of the third ventricle using the QIAamp DNA FFPE Tissue Kit (Qiagen). Genomic DNA was also extracted from leukocytes in a peripheral blood sample from one of the patients and a non-neoplastic gastric biopsy specimen from one of the patients. Capture-based next-generation DNA sequencing was performed at the University of California, San Francisco Clinical Cancer Genomics Laboratory, using an assay that targets all coding exons of approximately 500 cancer-related genes, select introns of 47 genes, and TERT promoter with a total sequencing footprint of 2.8 Mb (UCSF500 Cancer Panel). Sequencing libraries were prepared from genomic DNA, and target enrichment was performed by hybrid capture using a custom oligonucleotide library (Nimblegen SeqCap EZ Choice). Captured libraries were sequenced as paired-end 100 bp reads on an Illumina HiSeq 2500 instrument. Duplicate sequencing reads were removed computationally to allow for accurate allele frequency determination and copy number calling.

  Dataset EGAD00001003818

• Ovarian Cancer Organoid Biobank

  WGS of ovarian cancer organoids, tumor samples and blood references. Ovarian cancer (OC) is a heterogeneous disease usually diagnosed at a late stage. Experimental in vitro models that faithfully capture the hallmarks and tumor heterogeneity of OC are limited and hard to establish. We present a novel protocol that enables efficient derivation and long-term expansion of OC organoids. Utilizing this protocol, we have established 56 organoid lines from 32 patients, representing the spectrum of ovarian neoplasms, including non-malignant borderline tumors, as well as mucinous, clear-cell, endometrioid, low- and high-grade serous carcinomas. OC organoids recapitulate histological and genomic features of the pertinent lesion from which they were derived, illustrating intra- and inter-patient heterogeneity, and can be genetically modified. We show that OC organoids can be used for drug screening assays and capture different tumor subtype responses to the gold standard platinum-based chemotherapy, including acquisition of chemoresistance in recurrent disease. Finally, OC organoids can be xenografted, enabling in vivo drug sensitivity assays. Taken together, this demonstrates their potential application for research and personalized medicine.

  Dataset EGAD00001004387

• Subclonal diversification of primary breast cancer

  Cancers are ecosystems of genetically related clones, competing across space and time for limited resources. To understand the clonal structure of primary breast cancer, we applied genome and targeted sequencing to 295 samples from 49 patients’ tumors. The extent of subclonal diversification varied considerably among patients and encompassed many spatial patterns, including local growth, intraductal dissemination and clonal intermixture. Landmarks of disease progression, such as acquiring invasive or metastatic potential, arose within detectable subclones of antecedent lesions, suggesting that subclonal mutations could be relevant if actionable. No defined temporal order of mutation was evident, with the commonest genes, including PIK3CA, TP53, BRCA2, PTEN and MYC, mutated early in some, late in others, often exhibiting parallel evolution across subclones. Signatures of homologous recombination deficiency correlated with response to neoadjuvant chemotherapy. Thus, the interplay of mutation, growth and competition drives clonal structures of breast cancer that are complex, variable across patients and clinically relevant.

  Dataset EGAD00001000965

• Genome and transcriptome sequence data from a metastatic breast cancer patient

  Genome and transcriptome sequence data from a metastatic breast cancer patient, generated as part of the BC Cancer Agency's Personalized OncoGenomics (POG) study

  Dataset EGAD00001004902

• Genome and transcriptome sequence data from a metastatic gastric cancer patient

  Genome and transcriptome sequence data from a metastatic gastric cancer patient, generated as part of the BC Cancer Agency's Personalized OncoGenomics (POG) study

  Dataset EGAD00001004904

• Genome and transcriptome sequence data from a metastatic breast cancer patient

  Genome and transcriptome sequence data from a metastatic breast cancer patient, generated as part of the BC Cancer Agency's Personalized OncoGenomics (POG) study

  Dataset EGAD00001004910

• Genome and transcriptome sequence data from a metastatic breast cancer patient

  Genome and transcriptome sequence data from a metastatic breast cancer patient, generated as part of the BC Cancer Agency's Personalized OncoGenomics (POG) study

  Dataset EGAD00001004923

• Genome and transcriptome sequence data from a metastatic rectal cancer patient

  Genome and transcriptome sequence data from a metastatic rectal cancer patient, generated as part of the BC Cancer Agency's Personalized OncoGenomics (POG) study

  Dataset EGAD00001004918

• Genome and transcriptome sequence data from a metastatic breast cancer patient

  Genome and transcriptome sequence data from a metastatic breast cancer patient, generated as part of the BC Cancer Agency's Personalized OncoGenomics (POG) study

  Dataset EGAD00001004915