Exome-seq of cervical small cell neuroendocrine tumors
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB12274 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR1198360.fastq.gz | Fastqsanger.gz | |||
| ERR1198361.fastq.gz | Fastqsanger.gz | |||
| ERR1198362.fastq.gz | Fastqsanger.gz | |||
| ERR1198363.fastq.gz | Fastqsanger.gz | |||
| ERR1198364.fastq.gz | Fastqsanger.gz |
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Project description:Raw data of exome sequencing of 17 paired samples and 1 orphan tumor sample, total 18 samples
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Project description:Small intestinal neuroendocrine tumors (SI-NETs) arise from serotonin-producing enterochromaffin cells. SI-NETs are often well-differentiated tumors and most patients have regional or distant metastases at initial presentation. MicroRNAs (miRs) are post-transcriptional regulators which are important in diverse biological processes and can function as tumor suppressor genes or oncogenes. This study aims to identify an exclusive SI-NETs miR profile that may have a critical role in development, diagnosis, prognosis and progression of these malignancies. Five human NET cell lines, one octreotide-treated CNDT2.5 cells, one microdissected normal enterochromaffin cells, three snap-frozen normal ileum specimens and 15 SI-NET specimens at different stage of malignancy, five primary tumors, five mesentery metastases and five liver metastases, were included in this study. Total RNA was hybridized onto Affymetrix GeneChipM-BM-. miR arrays for genome-wide profiling. Array data summarization, normalization, and quality control were performed using miRNA QC Tool software.
2013-03-01 | E-GEOD-33568 | biostudies-arrayexpress
Project description:Cervical small cell neuroendocrine tumors (CSCNETs) are rare, aggressive neuroendocrine tumors (NETs). Reliable diagnostic and prognostic CSCNET markers are lacking, making diagnosis and prognosis prediction difficult, and treatment strategies limited. Here we provide mutation profiles for five tumor-normal paired CSCNETs using whole exome sequencing (WES). We expanded our assessment of frequently mutated genes to include publicly available data from 55 small intestine neuroendocrine tumors, 10 pancreatic neuroendocrine tumors, 42 small cell lung cancers, six NET cell lines, and 188 cervical cancers, along with our five CSCNETs. We identified 1,968 somatic mutations, including 1,710 missense, 106 nonsense, 144 splice site, 4 lncRNA, 3 nonstop, and 1 start codon mutation. We assigned functions to the 114 most frequently mutated genes based on gene ontology. ATRX, ERBB4, and genes in the Akt/mTOR pathway were most frequently mutated. Positive cytoplasmic ERBB4 immunohistochemical staining was detected in all CSCNET tumors tested, but not in adjacent normal tissues. To our knowledge, this study is the first to utilize WES in matched CSCNET and normal tissues to identify somatic mutations. Further studies will improve our understanding of how ATRX and ERBB4 mutations and AKT/mTOR signaling promote CSCNET tumorigenesis, and may be leveraged in novel anti-cancer treatment strategies.
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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: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:<p>The diagnosed incidence of small bowel neuroendocrine tumors (NETs) is increasing. While patients with localized disease can be treated surgically, those with metastatic disease currently have few treatment options. The success of biologically targeted therapies in other malignancies has led to interest in the molecular alterations underlying the pathogenesis of these NETs. To identify genetic aberrations in small intestine NETs, we generated copy number profiles from 31 primary and metastatic tumors and performed whole-exome sequencing on a subset of 29 primary small intestine NETs and 24 metastatic NETs in parallel with normal blood DNA. Whole-genome sequencing data was generated on 15 tumor/normal pairs and 5 primary/metastasis/normal trios. The global genetic landscape of small bowel NETs is relatively quiet. Consistent with previous studies, the overwhelming majority of tumors were characterized by loss of chromosome 18 and, to a lesser extent, other chromosome arm gains and losses. In stark contrast to arm-level alterations, recurrent high-level focal amplifications and deletions were much less prevalent in these tumors. High-throughput mutation screening and exome sequencing revealed similarly low rates of somatic mutation in NETs (median of 0.77 non-silent mutations per megabase (Mb) of coding DNA) compared to other recent cancer exome sequencing efforts. Our analysis of this cohort identified only a single, statistically significant recurrent somatic mutation targeting the cyclin-dependent kinase inhibitor gene, CDKN1B, encoding p27. </p>
| phs000579.v1.p1 | EGA
Project description:Of the multiple anatomical sites represented in oral cancer, squamous cell carcinoma of the tongue (TSCC) shows the highest incidence among younger age group. Chewing betel leaf, areca nut & slaked lime and smoking tobacco are common practises in India which have direct clinical implication in TSCC carcinogenesis. Here, for the first time we define the landscape of genomic alterations in TSCC from the Indian diaspora which would help to identify novel therapeutic targets for clinical intervention and define the genetic basis for TSCC. We performed high throughput sequencing of fifty four tongue samples using whole exome sequencing (n=47, 23 paired normal tumor and 1 unpaired) and transcriptome sequencing (n=17, 10 tumor and 5 normal). Mutation, copy number analysis were carried out using exome sequencing data and transcriptome analysis provided expressed genes and transcript fusions in tongue cancer patients. Further, integrated analysis were performed to identify biologically relevant alterations. Our preliminary analysis revealed presence of most frequently altered mutations in TSCC which includes mutations in TP53, NOTCH1, CDKN2A, USP6, KMT2D etc, consistent with literature. We observed high frequency of CG/T(GC/A) transversions in non-CpG islands, a signature associated with tobacco exposure. Somatic copy number analysis revealed copy number gain in known hallmarks such as CCND1, MYC, ORAOV1 genes along with copy number alteration in novel genes. Significant positive correlation was observed in the genes harbouring copy number gains and showing increased expression.
2018-05-31 | E-MTAB-4653 | biostudies-arrayexpress
Project description:Background: Whole exome sequencing (WES) has been proven to serve as a valuable basis for various applications such as variant calling and copy number variation (CNV) analyses. For those analyses the read coverage should be optimally balanced throughout protein coding regions at sufficient read depth. Unfortunately, WES is known for its uneven coverage within coding regions due to GC-rich regions or off-target enrichment. Results: In order to examine the irregularities of WES within genes, we applied Agilent SureSelectXT exome capture on human samples and sequenced these via Illumina in 2x101 paired-end mode. As we suspected the sequenced insert length to be crucial in the uneven coverage of exome captured samples, we sheared 12 genomic DNA samples to two different DNA insert size lengths, namely 130 and 170 bp. Interestingly, although mean coverages of target regions were clearly higher in samples of 130 bp insert length, the level of evenness was more pronounced in 170 bp samples. Moreover, merging overlapping paired-end reads revealed a positive effect on evenness indicating overlapping reads as another reason for the unevenness. In addition, mutation analysis on a subset of the samples was performed. In these isogenic subclones almost twofold mutations were failed in the 130 bp samples when compared to the 170 bp samples. Visual inspection of the discarded mutation sites exposed low coverages at the sites embedded in high amplitudes of coverage depth in the affected region. Conclusions: Producing longer insert reads could be a good strategy to achieve better uniform read coverage in coding regions and hereby enhancing the effective sequencing yield to provide an improved basis for further variant calling and CNV analyses.
2016-07-28 | E-MTAB-4527 | biostudies-arrayexpress
Project description:Background and Aims Small intestinal neuroendocrine tumours (SINETs) are the commonest malignancy of the small intestine; however underlying pathogenic mechanisms remain poorly characterised. Whole genome and exome sequencing has demonstrated that SINETs are mutationally quiet with the most frequent known mutation in the cyclin dependent kinase inhibitor 1B gene (CDKN1B) occurring in only ~8% of tumours, suggesting that alternative mechanisms may drive tumourigenesis. The aim of this study is to perform genome-wide molecular profiling of SINETs in order to identify pathogenic drivers based on molecular profiling. This study represents the largest unbiased integrated genomic, epigenomic, and transcriptomic analysis undertaken in this tumour type. Methods Here we present data from integrated molecular analysis of SINETs (n=97) including whole exome or targeted CDKN1B sequencing (n=29), HumanMethylation450 BeadChip (Illumina) array profiling (n=69), methylated DNA immunoprecipitation sequencing (n=16), copy number variance analysis (n=47) and Whole Genome-DASL (Illumina) expression array profiling (n=43). Results Based on molecular profiling SINETs can be classified in to three groups which demonstrate significantly different progression-free survival after resection of primary tumour (not reached at 10 years vs 56 months vs 21 months, p=0.04). Epimutations were found at a recurrence rate of up to 85% and 21 epigenetically dysregulated genes were identified, including CDX1 (86%), CELSR3 (84%), FBP1 (84%) and GIPR (74%). Conclusions This is the first comprehensive integrated molecular analysis of SINETs. We have demonstrated that these tumours are highly epigenetically dysregulated. Furthermore, we have identified novel molecular subtypes with significant impact on progression free survival. Background and Aims Small intestinal neuroendocrine tumours (SINETs) are the commonest malignancy of the small intestine; however underlying pathogenic mechanisms remain poorly characterised. Whole genome and exome sequencing has demonstrated that SINETs are mutationally quiet with the most frequent known mutation in the cyclin dependent kinase inhibitor 1B gene (CDKN1B) occurring in only ~8% of tumours, suggesting that alternative mechanisms may drive tumourigenesis. The aim of this study is to perform genome-wide molecular profiling of SINETs in order to identify pathogenic drivers based on molecular profiling. This study represents the largest unbiased integrated genomic, epigenomic, and transcriptomic analysis undertaken in this tumour type. Methods Here we present data from integrated molecular analysis of SINETs (n=97) including whole exome or targeted CDKN1B sequencing (n=29), HumanMethylation450 BeadChip (Illumina) array profiling (n=69), methylated DNA immunoprecipitation sequencing (n=16), copy number variance analysis (n=47) and Whole Genome-DASL (Illumina) expression array profiling (n=43). Results Based on molecular profiling SINETs can be classified in to three groups which demonstrate significantly different progression-free survival after resection of primary tumour (not reached at 10 years vs 56 months vs 21 months, p=0.04). Epimutations were found at a recurrence rate of up to 85% and 21 epigenetically dysregulated genes were identified, including CDX1 (86%), CELSR3 (84%), FBP1 (84%) and GIPR (74%). Conclusions This is the first comprehensive integrated molecular analysis of SINETs. We have demonstrated that these tumours are highly epigenetically dysregulated. Furthermore, we have identified novel molecular subtypes with significant impact on progression free survival. This study included 97 tumour samples from 85 individuals, this included both primary and metastatic tumour samples. 25 normal small intestinal samples were analysed.
2016-07-03 | E-GEOD-73832 | biostudies-arrayexpress