5735 results for "canc*"

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• Somatic_mutation_and_clonal_evolution_in_the_human_pancreas___WGS

  In this study we aim to characterise the landscape of mutation and clonal selection in the human pancreas. The study combines targeted sequencing and whole-genome sequencing of microbiopsies from the pancreas. The range of patients studied will include healthy individuals, both smokers and non-smokers, and patients with pancreatic ductal adenocarcinoma.

  Study EGAS00001002626

• Identification_of_synthetic_lethal_genes_by_CRISPR_Cas9_library

  Sequencing is performed on PCR products from the amplification of gRNA segments introduced into cell lines (some are commercial, some are derived by collaborators, as described in HMDMC 13/076). Cellular DNA or RNA are not sequenced. This data is defined as "Other Biological/Biochemical Assay Data" under the WTSI datasharing guidelines and consequently will be released at the time of publication and/or through faculty websites. SEQUENCING DETAILS: in October 2016 3 DNA samples will be submitted for PCR amplification and purification through CGP pipeline using Thompson's custom primer set and PCR settings and sequencing with Hiseq using a custom protocol (with 3 forward reads to read sgRNA1, sgRNA2 and the index, optimized with Illumina Bespoke Sanger team); read length 50bp. The following set of samples will be submitted in later 2016 and ealry 2017 as cell pellet to be processed through CGP Cas9 pipeline (Thompson's oligos and protocols) and sequences on Hiseq (same custom sequencing protocol described above) We are utilizing a custom CRISPR/Cas9 library to identify synthetic lethal gene pairs. Cells will be transduced with LV expressing Cas9, then infected with LV expressign the library of 42'000 sgRNA pairs. Cell pellet will be collected from the cell population at different timepoints. The samples will be processed by CGP pipeline customized for the specific protocol and then sequenced to identify the 19bp of the sgRNA and quantify their representation.

  Study EGAS00001002117

• Whole_Exome_PC9_and_A375

  Drug resistant population of PC9(human non-small cell lung cancer) or A375 (human melanoma) cell lines were used for this study. By exome sequencing, we will analyse mutations of cells in drug tolerent state and after drug holiday.

  Study EGAS00001002493

• Automated system for scoring hematoxylin and eosin-stained ovarian cancer sections by identifying single cells uncovered that stromal cell ratio is a significant predictor for overall survival and progression-free survival.

  Concerted efforts in genomic studies have revealed profound insights in prognostic ovarian cancer subtypes. On the other hand, abundant histology slides have been generated to date, yet their uses remain very limited and largely qualitative. Our goal is to develop automated histology analysis as an alternative subtyping technology for ovarian cancer that is cost-efficient and do not rely on DNA quality. We develop an automated system for scoring hematoxylin and eosin-stained (H&E) primary tumour sections of 91 late-stage ovarian cancer to identify single cells including cancer and stromal cells. We demonstrated high accuracy of our system based on expert pathologists’ scores (cancer=97.1%, stromal=89.1%) as well as compared to immunohistochemistry scoring (correlation=0.87). Quantitative stromal cell ratio is significantly associated with poor overall survival after controlling for clinical parameters including debulking status and age (multivariate analysis p=0.0021, HR=2.54, CI=1.40-4.60) and progression-free survival (multivariate analysis p=0.022, HR=1.75, CI=1.09–2.82). We demonstrate how automated image analysis enables objective quantification of microenvironmental composition of ovarian tumours. Our analysis reveals a strong effect of the tumour microenvironment on ovarian cancer progression and highlights the potential of therapeutic interventions that target the stromal compartment or cancer-stroma signalling in the stroma-high, late-stage ovarian cancer subset.

  Study EGAS00001001694

• Microdissection_sequencing_of_normal_human_prostate

  Histology sections from pathologically benign human prostates were prepared and microdissections retrieved from Laser-Capture Microdissection are submitted to low-input whole-genome sequencing.

  Study EGAS00001003049

• Investigation_of_mutational_signatures_associated_with_DNMT3A_deficiency_

  Mutational signatures have been shown to be attributable to specific genetic contexts, such as mutations in DNA repair genes. DNMT3A is a DNA methyltransferase that helps maintain the DNA methylation pattern in a site-specific manner and may participate in DNA repair or the stress response. We have identified an adult individual who is a germline mosaic for a DNMT3A mutation. We have obtained clonal lymphoblastoid cells (LCLs) from the subject representing both WT and mutant lines grown in the same individual for >50 years. These clones represent a unique opportunity to examine the mutational impact of the DNMT3A mutation in a well-controlled setting. Our goal is to perform WGS on whole blood, representing the pool, as well as several WT and several mutant clones, in order to investigate the contribution of DNMT3A to mutation rates and signatures.

  Study EGAS00001002329

• 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

• Differential Presence of Exons in Cell-Free DNA Reveals Different Patterns in Colorectal Cancer Between Metastatic and Non-Metastatic Patients

  Tumor genotyping during disease follow-up is gaining an increasing interest for monitoring and clinical management in colorectal cancer (CRC). Growing evidences suggest that single biopsies are inefficient for molecular profiling, due to clonal evolution and intratumoral heterogeneity of primary tumors and/or metastasis. Circulating free DNA (cfDNA) has emerged as an alternative source of genetic material that seems to be representative of the continuously changing tumor molecular features. Thus, the so-called 'liquid biopsy' also offers the additional advantages of accessibility and non-invasiveness for the patient. Novel strategies based on next-generation sequencing (NGS) of cfDNA are being currently developed, with most studies focusing on targeted deep sequencing panels of potential clinically actionable genes. Here we describe an alternative approach, consisting of exome-sequencing in cfDNA at a relatively shallower depth to provide a more general overview of the circulating genome. In this study, two groups of colorectal cancer patients, with either disseminated (M) or localized disease (N), were compared using whole-exome sequencing and a RNA-seq bioinformatics analysis pipeline. Thus, a set of 379 exons present at different levels in cfDNA from both groups were identified, giving rise to a completely new concept in this field, termed as 'Differential Presence of Exons'. Differentially present exons (DPEs) were subsequently used for M and N patients clustering and classification, allowing for the design of a predictive algorithm with encouraging preliminary results in a small subset of patients that could not be initially classified attending to the selection criteria (U group, unassignable).

  Study EGAS00001002687

• DERMATLAS__Porocarcinoma_WES

  Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis. Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles. The cases in this cohort are porocarcinomas.

  Study EGAS00001005720

• Sequencing_of_patient_samples_who_received_immune_checkpoint_inhibition___WES___NKI

  DNA and RNA isolated from FFPE blocks of patients who received immune checkpoint inhibition (ICI) are sequenced with the aim to identify therapeutically tractable vulnerabilities in tumors to prevent ICI resistance.

  Study EGAS00001003154