7411 results for "canc*"

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• Processing of tissue and cfDNA samples of CRC patients using Active-seq

  In this study, we have developed a novel technology called Active-Seq (Azide Click Tagging for In Vitro Epigenomic sequencing), a base conversion-free technology used to profile the DNA methylation status of a sample, based on the isolation of DNA containing unmodified CpG sites using a mutated bacterial methyltransferase enzyme and a synthetically prepared cofactor analogue. We procured samples from colorectal cancer (CRC) patients including tumour tissue as well as normal adjacent tissues. The data enabled us to identify CRC-specific markers that could then be used to track and monitor the presence of tumour DNA in cell-free DNA plasma (cfDNA) samples procured in the same patients. The FASTQ files of all the colorectal cancer tissues, normal adjacent tissues as wells as the cfDNA samples are available in this submission. The data made available in this study have been used to outline an approach for tumour-informed disease profiling in colorectal cancer cfDNA samples using Active-Seq.

  Study EGAS50000001226

• Biological and Therapeutic Implications of a Unique Subtype of NPM1 Mutated AML

  Study EGAS00001004872

• Single-cell RNA-seq profiling of patient derived organoids

  The aim of this study was to profile developement of resistance to cancer treatments using organoids. Two patient derived colorectal cancer organoids were profiled using single cell RNAseq after treatment with a combination of different anticancer drugs. The organoids were profiled both after 4 weeks of treatment and after a drug holiday of 2 weeks.

  Study EGAS50000001025

• _WGS__Somatic_mutation_in_skin_epidermis__SMS_

  Previously we have sequenced 2mm2 biospies of human epithelia at high depth using a custom bait set. This has identified a range of mutations. Some of the biospies are predicted to be clonal and we would like to perform WGS to give an insight into mutational burden, and CNV which may be associated with these mutations.

  Study EGAS00001004464

• Axes of Biological Variation in Diffuse Large B-Cell Lymphoma

  To explore the DLBCL molecular and genetic environment, we conducted genome-wide NGS sequencing on 103 DLBCL biopsy samples (named as Cornell-NCI cohort) with NGS platforms, including bulk WES, etc. The raw fastq files of the bulk WES were deposited on the EGA for user access. For additional information regarding the genomic data associated with the study, please also see the paper companion website at https://llmpp.ccr.cancer.gov/local/DLBCL_singlecell/

  Study EGAS50000001227

• CHEK2 molecular manuscript

  This study investigated the molecular landscape of 17 tumors from 9 individuals with biallelic germline pathogenic variants in CHEK2. Tumors included breast and non-breast cancers, and WES and sWGS bam files from the tumors are included in this submission. WES data was aligned to GRCh37 and sWGS data to GRCh38.

  Study EGAS50000000080

• WGS_skin_punches

  We wish to understand the degree of copy number alterations in normal human sun exposed skin. We have collected small punches of epithelia and using a bait set design have shown the these span a clone. WGS will provide copy number information on these.

  Study EGAS00001004465

• RESOLVE_trial_targeted_sequencing_data

  RESOLVE: Abemaciclib + Letrozole +/_- Metformin, Zotatifin, or Gedatolisib in Endometrial or Low-Grade Serous Ovarian Cancer

  Study EGAS50000001202

• Tumour evolvability metrics predict recurrence in advanced localised prostate cancer (tumour data)

  Study EGAS00001006096

• HSC_population_dynamics___KX007_samples

  My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology. The four major questions I will address are: 1. How do age and aging affect normal human HSC dynamics in vivo? 2. How do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics? 3. Is response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood? 4. How are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?

  Study EGAS00001004193

• Characterization of UV DNA damage in B-cell precursor acute lymphoblastic leukemia

  Study EGAS00001008128

• Multi-Region WES of Metastatic Colorectal Cancer

  Study EGAS00001003573

• Detection of brain cancer using genome-wide cell-free DNA fragmentomes

  Diagnostic delays in patients with brain cancer are common and can impact patient outcome. Development of a blood-based assay for detection of brain cancers could accelerate brain cancer detection. In this study, we analyzed genome-wide cell-free (cfDNA) fragmentomes, including fragmentation profiles and repeat landscapes, from the plasma of individuals with (n=148) and without (n=357) brain cancer. Machine learning analyses of cfDNA fragmentome features detected brain cancer across all grade gliomas (AUC=0.90, 95% CI: 0.87-0.93) and these results were validated in an independent prospectively collected cohort. cfDNA fragmentome changes in patients with gliomas represented a combination of fragmentation profiles from glioma cells and altered white blood cell populations in the circulation. These analyses reveal the properties of cfDNA in patients with brain cancer and open new avenues for noninvasive detection of these individuals.

  Study EGAS50000000986

• Primary breast tumor heterogeneity through therapy

  We performed whole-exome sequencing on multiple regions (n=2-3) from four primary untreated breast tumors (n=1 HER2+, n=2 ER+/HER2-, n=1 triple-negative), as well as matched normal. We also performed whole-exome sequencing on one region from the pre-treatment diagnostic core biopsy and multiple regions (n=2-6) from the post-treatment surgical specimen for five HER2+ primary breast tumors, as well as matched normal; all were treated with combination chemotherapy and trastuzumab. Analysis of these specimens allows characterization of breast tumor heterogeneity and clonal evolution.

  Study EGAS00001003168

• Validation of a targeted sequencing panel for multiple myeloma

  Study EGAS00001006164

• Spatial predictors of response to immunotherapy in microsatellite stable metastatic colorectal cancer

  Microsatellite stable (MSS) colorectal cancers (CRC) are largely unresponsive to immune checkpoint inhibition (ICI), prompting investigation into strategies to enhance sensitivity. The MAYA trial, which utilized temozolomide (TMZ) in MGMT-silenced MSS mCRC, hypothesized that TMZ-induced hypermutation could sensitize tumors to ICI. This phase II trial met its primary endpoint, demonstrating durable clinical responses with TMZ combined with ipilimumab and nivolumab. To elucidate factors influencing response heterogeneity, we conducted multi-omic spatial profiling of samples from patients who participated in the MAYA trial, including baseline and on-treatment tissue and blood specimens. While increased neoantigen load following TMZ exposure did not consistently predict for deep responses, spatial profiling revealed key determinants. Lymphocyte proportions, particularly CD8+KI67+ cells, within stromal and tumor compartments, along with macrophage composition (CD68+CD163+ cells) at the tumor-stromal interface, were predictive of response. Treatment pressures dynamically altered the tumor microenvironment composition and activated peripheral immune cells. This study is the first to identify spatial predictors of response to this promising novel treatment approach for MSS CRC.

  Study EGAS50000001567

• Chromosomal instability shapes the tumor microenvironment of oesophageal adenocarcinoma via a cGAS–chemokine–myeloid axis

  This study employed whole-genome sequencing (WGS) to investigate genomic alterations in oesophagogastric adenocarcinoma, with a focus on mechanisms of chromosomal instability. Twelve tumour samples were analysed, including specimens obtained prior to neoadjuvant chemotherapy and at surgical resection. WGS was used to identify structural variants, quantify tumour mutational burden, and detect potential driver mutations across samples. The study aimed to correlate genomic measures of chromosomal instability with clinicopathological features to improve understanding of tumour biology.

  Study EGAS50000001561

• Massive Genomic Rearrangment Acquired in a Single Catastrophic Event During Cancer Development

  Cancer is driven by mutation. Using Agilent exome hybridisation capture and Illumina GA massively parallel sequencing technology, we aim to sequence ~1600 microRNAs plus the protein coding genome of 25 matched human renal cancer samples. Bespoke algorithms are being developed to identify the somatically acquired point mutations, insertions and deletions in these samples. This project will give unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with renal cancer development.Agilent whole exome hybridisation capture will be performed on genomic DNA derived from 25 renal cancers and matched normal DNA from the same patients. Three lanes of Illumina GA sequencing will be performed on the resulting 50 exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes.

  Study EGAS00000000029

• A small cell lung cancer genome reports complex tobacco exposure signatures

  Cancer is driven by mutation. Worldwide, tobacco smoking is the major lifestyle exposure that causes cancer, exerting carcinogenicity through 60 chemicals that bind and mutate DNA. Using massively parallel sequencing technology, we sequenced a small cell lung cancer cell line, NCI-H209, to explore the mutational burden associated with tobacco smoking. 22,910 somatic substitutions were identified, including 132 in coding exons. Multiple mutation signatures testify to the cocktail of carcinogens in tobacco smoke and their proclivities for particular bases and surrounding sequence context. Effects of transcription-coupled repair and a second, more general expression-linked repair pathway were evident. We identified a tandem duplication that duplicates exons 3-8 of CHD7 in-frame, and another two lines carrying PVT1-CHD7 fusion genes, suggesting that CHD7 may be recurrently rearranged in this disease. These findings illustrate the potential for next-generation sequencing to provide unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with cancer.

  Study EGAS00000000051

• Various_Cancer_Fusion_Gene_Sequencing

  Genomic libraries (500 bps) will be generated from total genomic DNA derived from 50 commomon epithelial cancer samples and subjected to total of eight lanes of 37 bp, paired end sequencing on the llumina GA. 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 EGAS00001000012

• The patterns and dynamics of genomic instability in metastatic pancreatic cancer

  Pancreatic cancer is an aggressive malignancy with a five-year mortality of 97–98%, usually due to widespread metastatic disease. Previous studies indicate that this disease has a complex genomic landscape, with frequent copy number changes and point mutations, but genomic rearrangements have not been characterized in detail. Despite the clinical importance of metastasis, there remain fundamental questions about the clonal structures of metastatic tumours, including phylogenetic relationships among metastases, the scale of ongoing parallel evolution in metastatic and primary sites, and how the tumour disseminates. Here we harness advances in DNA sequencing to annotate genomic rearrangements in 13 patients with pancreatic cancer and explore clonal relationships among metastases. We find that pancreatic cancer acquires rearrangements indicative of telomere dysfunction and abnormal cell-cycle control, namely dysregulated G1-to-S-phase transition with intact G2–M checkpoint. These initiate amplification of cancer genes and occur predominantly in early cancer development rather than the later stages of the disease. Genomic instability frequently persists after cancer dissemination, resulting in ongoing, parallel and even convergent evolution among different metastases. We find evidence that there is genetic heterogeneity among metastasis-initiating cells, that seeding metastasis may require driver mutations beyond those required for primary tumours, and that phylogenetic trees across metastases show organ-specific branches. These data attest to the richness of genetic variation in cancer, brought about by the tandem forces of genomic instability and evolutionary selection.

  Study EGAS00000000064

• CLL_Cancer_Whole_Genome_Sequencing

  Genomic libraries (500 bps) will be generated from total genomic DNA derived from a range of cancer samples and subjected paired end sequencing on the llumina GA. 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 EGAS00001000014

• TMD_AMLK_Exome_Study

  Agilent whole exome hybridisation capture will be performed on genomic DNA derived from 20 Primary Acute Megakaryocytic Leukemia samples and matched normal DNA from the same patients. Three lanes of Illumina GA sequencing will be performed on the resulting 100 exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes

  Study EGAS00001000027

• Recurrent somatic DICER1 mutations in non-epithelial ovarian tumors

  Background: Germline truncating mutations in DICER1, an RNase III-type endoribonuclease essential for processing of microRNAs, are seen in families with the pleuropulmonary blastoma-family tumor and dysplasia syndrome; these individuals have a propensity to develop non-epithelial ovarian tumors (i.e. sex-cord stromal and germ cell tumors). Methods: We sequenced the whole transcriptomes or exomes of 14 non-epithelial ovarian tumors and noted closely clustered mutations in the RNase IIIb domain of DICER1 in four cases. Using Sanger sequencing, we then analyzed additional ovarian tumors for mutations in this region. The impact of the mutations on the enzymatic activity of Dicer1 was determined using in vitro RNA cleavage assays. Results: RNase IIIb domain DICER1 mutations were found in 30/102 non-epithelial ovarian tumors (29%), predominantly Sertoli-Leydig cell tumors (26/43, 60%), including 4/4 from individuals with germline DICER1 mutations. The mutations were restricted to metal binding sites within the RNase IIIb catalytic centres critical for miRNA interaction and cleavage, and were somatic in all 14 cases where germline DNA was available for testing. Of 266 epithelial ovarian and endometrial cancers tested, one case, an ovarian carcinosarcoma, had a hotspot mutation. In vitro, the mutant DICER proteins showed reduced RNase IIIb activity but retained RNase IIIa activity. Conclusions: Somatic missense mutations of the RNase IIIb domain of DICER1 are common in non-epithelial ovarian tumors. Genetic, pathologic, and functional evidence suggest that these mutations do not obliterate DICER1 function, rather, they alter it in specific cell types, a novel mechanism through which perturbed microRNA expression is oncogenic.

  Study EGAS00001000135

• μSeq: Universal mutation rate quantification via deep sequencing of a single clonal expansion

  We use patient-derived colorectal cancer organoids to introduce µSeq, a universal framework for inferring mutation rates in diverse biological systems. Our approach extracts mutation rates from deep sequencing of single clonal expansions, with a time gain of tenfold or more compared to a mutation-accumulation line, at the cost of three billion read whole-genome sequencing.

  Study EGAS50000001761