Heterogeneous immune and tumor clonal evolution patterns in liver cancer
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Qiagen DNAeasy blood and tissue kit, Illumina NovaSeq 6000, Illumina TrueSeq Exome Kit
ORGANISM(S): Homo sapiens
SUBMITTER: Bojan Losic
PROVIDER: E-MTAB-8127 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Whole exome sequencing of 5 MDS/MPN patients to identify the target of chromosome 22 acquired uniparental disomy (22aUPD). For samples E4051 and E6523, peripheral blood leucocytes (tumour) and cultured T-cells (germline) were prepared for exome sequencing using the Agilent SureSelect kit (Agilent Technologies, Palo Alto, CA, USA) (Human All Exon 50 Mb) and then sequenced on an Illumina HiSeq 2000 (Illumina, Great Abington, UK) at the Wellcome Trust Centre for Human Genetics, Oxford, UK. For samples ULSAM1182, ULSAM1242 and ULSAM1356, peripheral blood leukocyte DNA only were exome sequenced by SciLifeLab (Stockholm, Sweden).
2019-01-22 | E-MTAB-7491 | biostudies-arrayexpress
Project description:Heterogeneous immune and tumor clonal evolution patterns in liver cancer
| PRJEB33424 | ENA
Project description:Triple Negative Breast Cancer (TNBC) is an aggressive subtype of breast cancer with high intra-tumoral heterogeneity, frequently resistant to treatment and no known targeted therapy available to improve patient outcomes. It has been hypothesized that the genomic architecture of a TNBC tumour evolves over time, both before, and during therapy, leading to therapy resistance and a high propensity to relapse. Whether this is an inherent property of the tumour or acquired over time is not well characterized. Despite this important clinical implication, limited studies have been carried out to unravel temporal evolution of TNBC over time. Herein, we report an OMICS based analysis of three TNBC patients who were longitudinally sampled during their treatment at different times of relapse. We recruited three TNBC patients at the time of their first relapse who were then followed-up through the course of their treatment. We obtained retrospective samples (tumour samples) from patient tumours at diagnosis (before neo-adjuvant chemotherapy - NACT) at surgery (post NACT) and prospectively sampled them at each subsequent relapse (tumour, blood plasma, and buffy coat) as determined by RECIST criteria. Tumor and buffy coat DNA were subjected to whole exome sequencing (WES) at 200x, and SNP arrays for copy number variation (CNV) analysis. RNA from tumour samples at relapse was subjected to whole transcriptome sequencing. Pathogenic germline BRCA1 variants identified in WES were validated using Sanger sequencing. 1084 somatic mutations identified in whole exome sequencing of all tumour tissues (n=13) from three patients, were subjected to a custom amplicon ultra-deep sequencing assay at 30,000X in their germline DNA (n=3), tumour DNA (n=10), and cfDNA from plasma samples at relapse (n=8). Copy number corrected allele frequencies, tumour ploidy, tumour purity, and ultra-deep sequencing assay derived variant allele frequencies were used to infer clonal and phylogenetic architecture of each patient as it evolved under selective pressure of therapy over time. Clonality analysis incorporating allele fractions from ultra-deep sequencing identified clones comprising of mutations that are present throughout the course of therapy which we term as founding clones and stem mutations respectively. Such founding clones comprising of stem mutations in all 3 patients were present throughout the course of treatment, irrespective of change in treatment modalities. These stem clones included well characterized cancer related genes like PDGFRB & ARID2 (Patient 02), TP53, BRAF & CSF3R (Patient 04) and ESR1, APC, EZH2 & TP53 (Patient 07). Such branching evolution is seen in all three patients wherein the dominant clone (stem clone) acquires additional mutations to form sub-clones, while persisting over time. These sub-clones may be chemo and radio resistant, while also providing for organ specific metastatic potential. Allele fractions of expressed variants inferred from RNA-Seq data co-related with allele fractions from WES data indicating that all somatic.
2023-08-18 | E-MTAB-11376 | biostudies-arrayexpress
Project description:Single Gland Whole-exome sequencing: building on our prior description of multi-region WES of colorectal tumors and targeted single gland sequencing (E-MTAB-2247), we performed WES of multiple single glands from different sides (right: A and left: B) of two tumors in this study (tumor O and U) on the illumina platform using the Agilent SureSelect 2.0 or illumina Nextera Rapid Capture Exome kit (SureSelect or NRCE, as indicated in the naming of fastq files). Colorectal Cancer Xenograft Whole-exome sequencing: The HCT116 and LoVo Mismatch-Repair-deficient colorectal adenocarcinoma cell lines were obtained from the ATCC and cultured under standard conditions. For both cell lines, a single âfoundingâ cell was cloned and expanded in vitro to ~6M cells. Two aliquots of ~1M cells were subcutaneously injected into opposite flanks (right and left) of a nude mouse and tumors allowed to reach a size of ~1B cells (1cm3) before the animal was sacrificed. Tumor tissue was collected separately from the right and left lesions and DNA was extracted for WES using the illumina TruSeq Exome kit or Nextera Rapid Capture Exome expanded Kits (Truseq or NRCEe), as was DNA from the first passage population (a polyclonal tissue culture for HCT116 and a polyclonal xenograft sample for LoVo), which were employed as a control to study mutation accumulation in culture and post xenotransplantation.
2017-05-01 | E-MTAB-5547 | biostudies-arrayexpress
Project description:In this study we performed proteogenomic analysis for 9 cell lines of malignant melanoma. The main objectives of the study were identifying the variants originating from point mutations and analyzing the effect of exome data filtering on the outcome of variant identification.
2018-12-05 | PXD007662 | Pride
Project description:Whole exome sequencing to determine whether acquisition of resistance to MK2206 in MDA-MB-361 is mediated by a new AKT1 mutation. Cells were exposed in vitro to drug for 12 weeks. Surviving cells were expanded for another 2 weeks in the presence of drug before sequencing.
2023-06-02 | E-MTAB-8066 | biostudies-arrayexpress
Project description:Intrahepatic cholangiocarcinoma (iCCA) is a fatal bile duct cancer with dismal prognosis and limited therapeutic options. By performing RNA- and exome sequencing analyses we have discovered a novel fusion event, FGFR2-PPHLN1 (16%), and damaging mutations in the ARAF oncogene (11%). Methods: mRNA and gDNA were exctracted from fresh frozen tumor tissues and corresponding normal tissue (n=8 pairs) from patients with iCCA who underwent surgical resection. RNA-seq was performed using Illumina HiSeq 2500 System with 100 nucleotide single-end reads. One sample and its paired non-tumoral tissue were eliminated from the subsequent analysis because of bad RNa quality. The same 8 paired tumors were also analyzed by whole-exome seq. Submitter confirms there are no patient privacy concerns with these data. This dataset is part of the TransQST collection.
2015-01-22 | E-GEOD-63420 | biostudies-arrayexpress
Project description:Whole exome sequencing was performed on set of 48 DNA samples obtained from 16 EGFR mutated NSCLC patients whose tumors progressed following EGFR-TKI treatment. The DNA samples included baseline biopsy, rebiopsy and blood from the same patient. By comparing the variants in rebiopsy tumors and baseline tumors we aim to understand the genomic alterations responsible for the development of EGFR-TKI resistance in NSCLC patients.
2022-02-11 | E-MTAB-11404 | biostudies-arrayexpress
Project description:Mutations in the nucleophosmin 1 (NPM1) gene are considered founder mutations in the pathogenesis of acute myeloid leukemia (AML). To further characterize the genetic composition of NPM1 mutated (NPM1mut) AML, we assess mutation status of five recurrently mutated oncogenes (FLT3, DNMT3A, IDH1, IDH2, NRAS) in 129 paired NPM1mut samples obtained at diagnosis and relapse. We find a substantial shift in the genetic pattern from diagnosis to relapse including NPM1mut loss (n=11). To gain further insight into these NPM1mut loss cases, we perform whole exome sequencing (WES) and RNA-Seq. At the time of relapse, NPM1mut loss patients (pts) feature distinct mutational patterns that shared almost no somatic mutation with the corresponding diagnosis sample and impact different signaling pathways including loss of characteristic NPM1mut associated gene expression patterns. In contrast, profiles of pts with persistent NPM1mut at relapse are reflected by a high overlap of mutations between diagnosis and relapse. Thus, our findings confirm that relapse often originates from persistent leukemic clones, though NPM1mut loss cases suggest a second “de novo” or treatment-associated AML (tAML) as alternative cause of “relapse" in a subgroup of cases.
2019-05-14 | GSE128603 | GEO
Project description:Mutations in the nucleophosmin 1 (NPM1) gene are considered founder mutations in the pathogenesis of acute myeloid leukemia (AML). To further characterize the genetic composition of NPM1 mutated (NPM1mut) AML, we assess mutation status of five recurrently mutated oncogenes (FLT3, DNMT3A, IDH1, IDH2, NRAS) in 129 paired NPM1mut samples obtained at diagnosis and relapse. We find a substantial shift in the genetic pattern from diagnosis to relapse including NPM1mut loss (n=11). To gain further insight into these NPM1mut loss cases, we perform whole exome sequencing (WES) and RNA-Seq. At the time of relapse, NPM1mut loss patients (pts) feature distinct mutational patterns that shared almost no somatic mutation with the corresponding diagnosis sample and impact different signaling pathways including loss of characteristic NPM1mut associated gene expression patterns. In contrast, profiles of pts with persistent NPM1mut at relapse are reflected by a high overlap of mutations between diagnosis and relapse. Thus, our findings confirm that relapse often originates from persistent leukemic clones, though NPM1mut loss cases suggest a second “de novo” or treatment-associated AML (tAML) as alternative cause of “relapse" in a subgroup of cases.
2019-05-14 | GSE128602 | GEO