Whole-exome sequencing of NTHL1 deficient tumors
Ontology highlight
ABSTRACT:
PROVIDER: EGAS00001003400 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:Studies of naturally occurring cancers in dogs, which share many genetic and environmental factors with humans, provide valuable information as a comparative model for studying the mechanisms of human cancer pathogenesis. While individual and small-scale studies of canine cancers are underway, more generalized multi-omics studies have not been attempted due to the lack of large-scale and well-controlled genomic data. Here, we produced reliable whole-exome and whole-transcriptome sequencing data of 197 canine mammary cancers and their matched controls, annotated with rich clinical and biological features. Our dataset provides useful reference points for comparative analysis with human cancers and for developing novel diagnostic and therapeutic technologies for cancers in pet dogs.
| S-EPMC6694171 | biostudies-literature
Project description:Somatic genetic alterations in pituitary neuroendocrine tumors (PitNET) tissues have been identified in several studies, but detection of overlapping somatic PitNET candidate genes is rare. We sequenced and by employing multiple data analysis methods studied the exomes of 15 PitNET patients to improve discovery of novel factors involved in PitNET development. PitNET patients were recruited to the study before PitNET removal surgery. For each patient, two samples for DNA extraction were acquired: venous blood and PitNET tissue. Exome sequencing was performed using Illumina NexSeq 500 sequencer and data analyzed using two separate workflows and variant calling algorithms: GATK and Strelka2. A combination of two data analysis pipelines discovered 144 PitNET specific somatic variants (mean = 9.6, range 0-19 per PitNET) of which all were SNVs. Also, we detected previously known GNAS PitNET mutation and identified somatic variants in 11 genes, which have contained somatic variants in previous WES and WGS studies of PitNETs. Noteworthy, this is the third study detecting somatic variants in gene RYR1 in the exomes of PitNETs. In conclusion, we have identified two novel PitNET candidate genes (AC002519.6 and AHNAK) with recurrent somatic variants in our PitNET cohort and found 13 genes overlapping from previous PitNET studies that contain somatic variants. Our study demonstrated that the use of multiple sequencing data analysis pipelines can provide more accurate identification of somatic variants in PitNETs.
| S-EPMC9417189 | biostudies-literature
Project description:Genomic technologies, such as whole-exome sequencing, are a powerful tool in genetic research. Such testing yields a great deal of incidental medical information, or medical information not related to the primary research target. We describe the management of incidental medical information derived from whole-exome sequencing in the research context. We performed whole-exome sequencing on a monozygotic twin pair in which only 1 child was affected with congenital anomalies and applied an institutional review board-approved algorithm to determine what genetic information would be returned. Whole-exome sequencing identified 79525 genetic variants in the twins. Here, we focus on novel variants. After filtering artifacts and excluding known single nucleotide polymorphisms and variants not predicted to be pathogenic, the twins had 32 novel variants in 32 genes that were felt to be likely to be associated with human disease. Eighteen of these novel variants were associated with recessive disease and 18 were associated with dominantly manifesting conditions (variants in some genes were potentially associated with both recessive and dominant conditions), but only 1 variant ultimately met our institutional review board-approved criteria for return of information to the research participants.
| S-EPMC3362899 | biostudies-other
Project description:Neuroblastoma is a pediatric tumor characterized by histologic heterogeneity, and accounts for ~15% of childhood deaths from cancer. The five-year survival for patients with high-risk stage 4 disease has not improved in two decades. We used whole exome sequencing (WES) to identify mutations present in three independent high-risk stage 4 neuroblastoma tumors (COA/UAB-3, COA/UAB -6 and COA/UAB -8) and a stage 3 tumor (COA/UAB-14). Among the four tumors WES analysis identified forty-three mutations that had not been reported previously, one of which was present in two of the four tumors. WES analysis also corroborated twenty-two mutations that were reported previously. No single mutation occurred in all four tumors or in all stage 4 tumors. Three of the four tumors harbored genes with CADD scores??20, indicative of mutations associated with human pathologies. The average depth of coverage ranged from 39.68 to 90.27, with?>99% sequences mapping to the genome. In summary, WES identified sixty-five coding mutations including forty-three mutations not reported previously in primary neuroblastoma tumors. The three stage 4 tumors contained mutations in genes encoding protein products that regulate immune function or cell adhesion and tumor cell metastasis.
| S-EPMC5736554 | biostudies-literature
Project description:Choroid plexus tumors (CPTs) are rare intracranial neoplasms, representing <1% of all brain tumors, yet they represent 20% of first-year pediatric brain tumors. Although these tumors have been linked to TP53 germline mutations in the context of Li-Fraumeni syndrome, their somatic driver alterations remain poorly understood. In this study, we report two cases of lateral ventricle tumors: 3-yr-old male diagnosed with an atypical choroid plexus papilloma (aCPP), and a 6-mo-old female diagnosed with a choroid plexus carcinoma (CPC). We performed whole-exome sequencing of paired blood and tumor tissue in both patients, categorized somatic variants, and determined copy-number alterations. Our analysis revealed a tier II variant (Association for Molecular Pathology [AMP] criteria) in BRD1, a H3 and TP53 acetylation agent, in the aCPP. In addition, we detected copy-number gains on Chromosomes 12, 18, and 20 and copy-number losses on Chromosomes 13q and 22q (BRD1 locus) in this tumor. The CPC tumor had only a pathogenic germline TP53 variant, based on American College of Medical Genetics (ACMG) criteria, with a clinical and familiar history of Li-Fraumeni syndrome. The CPC patient presented loss of heterozygosity (LoH) of TP53 loci and hyperdiploid genome. Both tumors were microsatellite-stable. This is the first study performing whole-exome sequencing in Brazilian choroid plexus tumors, and in line with the literature, we corroborate the absence of recurrent somatic mutations in these tumors. Further studies with larger sample sizes are necessary to confirm our findings and better understand the underlying biology of these tumors.
| S-EPMC10111795 | biostudies-literature
Project description:Most tumor samples are a heterogeneous mixture of cells, including admixture by normal (non-cancerous) cells and subpopulations of cancerous cells with different complements of somatic aberrations. This intra-tumor heterogeneity complicates the analysis of somatic aberrations in DNA sequencing data from tumor samples.We describe an algorithm called THetA2 that infers the composition of a tumor sample-including not only tumor purity but also the number and content of tumor subpopulations-directly from both whole-genome (WGS) and whole-exome (WXS) high-throughput DNA sequencing data. This algorithm builds on our earlier Tumor Heterogeneity Analysis (THetA) algorithm in several important directions. These include improved ability to analyze highly rearranged genomes using a variety of data types: both WGS sequencing (including low ?7× coverage) and WXS sequencing. We apply our improved THetA2 algorithm to WGS (including low-pass) and WXS sequence data from 18 samples from The Cancer Genome Atlas (TCGA). We find that the improved algorithm is substantially faster and identifies numerous tumor samples containing subclonal populations in the TCGA data, including in one highly rearranged sample for which other tumor purity estimation algorithms were unable to estimate tumor purity.
| S-EPMC4253833 | biostudies-other
Project description:Solitary fibrous tumors (SFTs) are rare mesenchymal tumors. Here, we describe the identification of a NAB2-STAT6 fusion from whole-exome sequencing of 17 SFTs. Analysis in 53 tumors confirmed the presence of 7 variants of this fusion transcript in 29 tumors (55%), representing a lower bound for fusion frequency at this locus and suggesting that the NAB2-STAT6 fusion is a distinct molecular feature of SFTs.
| S-EPMC3984043 | biostudies-literature
Project description:Neurofibromatosis type 1 (NF1) is a hereditary cancer predisposition syndrome characterized by frequent cutaneous and nervous system abnormalities. Patients with NF1 also have an increased prevalence of multiple gastrointestinal and peripancreatic neoplasms-neuroendocrine tumors of the ampulla that express somatostatin are particularly characteristic of NF1. In this study, we characterize the genetic alterations of a clinically well-characterized cohort of six NF1-associated duodenal neuroendocrine tumors using whole-exome sequencing. We identified inactivating somatic mutations in the NF1 gene in three of six tumors; the only other gene altered in more than one tumor was IFNB1. Copy number analysis revealed deletion/loss of heterozygosity of chromosome 22 in three of six patients. Analysis of germline variants revealed germline deleterious NF1 variants in four of six patients, as well as deleterious variants in other tumor suppressor genes in two of four patients with deleterious NF1 variants. Taken together, these data confirm the importance of somatic inactivation of the wild-type NF1 allele in the formation of NF1-associated duodenal neuroendocrine tumors and suggest that loss of chromosome 22 is important in at least a subset of cases. However, we did not identify any genes altered in the majority of NF1-associated duodenal neuroendocrine tumors that uniquely characterize the genomic landscape of this tumor. Still, the genetic alterations in these tumors are distinct from sporadic neuroendocrine tumors occurring at these sites, highlighting that unique genetic alterations drive syndromic tumors.
| S-EPMC6168403 | biostudies-literature
Project description:SummaryWhole-exome sequencing (WES) has extensively been used in cancer genome studies; however, the use of WES data in the study of loss of heterozygosity or more generally allelic imbalance (AI) has so far been very limited, which highlights the need for user-friendly and flexible software that can handle low-quality datasets. We have developed a statistical approach, ExomeAI, for the detection of recurrent AI events using WES datasets, specifically where matched normal samples are not available.AvailabilityExomeAI is a web-based application, publicly available at: http://genomequebec.mcgill.ca/exomeai.ContactJavadNadaf@gmail.com or somayyeh.fahiminiya@mcgill.caSupplementary informationSupplementary data are available at Bioinformatics online.
| S-EPMC4308664 | biostudies-literature
Project description:BackgroundThe genomic abnormalities associated with uterine leiomyosarcoma (uLMS) have not been fully elucidated to date.ObjectiveTo understand the pathogenesis of uLMS and to identify driver mutations and potential therapeutic targets in uLMS.MethodsThree matched tumor-constitutional DNA pairs from patients with recurrent uLMS were subjected to whole-exome capture and next-generation sequencing. The role of the selected gene SHARPIN in uLMS was analyzed by the CCK-8 assay and colony formation assay after specific siRNA knockdown.ResultsWe identified four genes with somatic SNVs, namely, SLC39A7, GPR19, ZNF717, and TP53, that could be driver mutations. We observed that 30.7% (4/13) of patients with uLMS had TP53 mutations as analyzed by direct sequencing. Analysis of somatic copy number variants (CNVs) showed regions of chromosomal gain at 1q21-23, 19p13, 17q21, and 17q25, whereas regions of chromosomal loss were observed at 2q35, 2q37, 1p36, 10q26, 6p22, 8q24, 11p15, 11q12, and 9p21. The SHARPIN gene was amplified in two patients and mutated in another (SHARPIN: NM_030974: exon2: c.G264C, p.E88D). Amplification of the SHARPIN gene was associated with shorter PFS and OS in soft tissue sarcoma, as shown by TCGA database analysis. Knockdown of SHARPIN expression was observed to decrease cell growth and colony formation in uterine sarcoma cell lines.ConclusionsExome sequencing revealed mutational heterogeneity of uLMS. The SHARPIN gene was amplified in uLMS and could be a candidate oncogene.
| S-EPMC8226214 | biostudies-literature