The genomic landscape of small intestine neuroendocrine tumors [CGH]
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE45190 | GEO | 2013/03/16
SECONDARY ACCESSION(S): PRJNA193189
REPOSITORIES: GEO
Similar Datasets
Project description:Small intestine neuroendocrine tumors are the commonest neuroendocrine tumors of the GI tract. Next gen sequencing of the whole exome was undertaken to identify SNPs and SCNA in these tumor samples. Subsequent bioinformatic anlaysis was done where the reads ratios of tumor/normal were log2 tranformed, segments indentified with DNAcopy (R package) and regions of SCNA were identified. Amplification of chr 4, 5, 14 and 20 was observed. The validation of these SCNAs was done with arrayCGH. The results of array CGH is in concordeance with the exome sequencing data. DNA from matched tumor and normal sample of SI-NETs was done by spin column method. Libraries were constructed and exome enriched for next gen sequencing. The same gDNA was hybridized with Cy5 and Cy3 and subsequent analysis was done. This study represents the CGH portion of the study.
2013-03-16 | E-GEOD-45190 | biostudies-arrayexpress
Project description:A powerful way to discover key genes playing causal roles in oncogenesis is to identify genomic regions that undergo frequent alteration in human cancers. We have reported high-resolution analyses of somatic copy-number alterations (SCNAs) from 3131 cancer specimens, belonging largely to 26 histological types. We identify 158 regions of focal SCNA that are altered at significant frequency across multiple cancer types, of which 122 cannot be explained by the presence of a known cancer target gene located within these regions. Several candidate genes and families are enriched among these regions of focal SCNA, including members of the BCL2 family of apoptosis regulators and the NF-κΒ pathway. We show that cancer cells harboring amplifications surrounding the MCL1 and BCL2L1 anti-apoptotic genes depend upon expression of these genes for survival. Finally, we demonstrate that a large majority of SCNAs identified in individual cancer types are present in multiple cancer types.
2010-02-18 | GSE19399 | GEO
Project description:We performed whole exome sequencing and copy number analysis for 15 triplets, each comprising normal colorectal tissue, primary colorectal carcinoma, and its synchronous matched liver metastasis. We analyzed the similarities and differences between primary colorectal carcinoma and matched liver metastases in regards to somatic mutations and somatic copy number alterationss (SCNAs). The genomic profiling demonstrated mutations in APC(73%), KRAS (33%), ARID1A and PIK3CA (6.7%) genes between primary colorectal and metastatic liver tumors. TP53 mutation was observed in 47% of the primary samples and 67% in liver metastatic samples. The grouped pairs, in hierarchical clustering showed similar SCNA patterns, in contrast to the ungrouped pairs. Many mutations (including those of known key cancer driver genes) were shared in the grouped pairs. The ungrouped pairs exhibited distinct mutation patterns with no shared mutations in key driver genes. Four ungrouped liver metastasis samples had mutations in DNA mismatch repair genes along with hypermutations and a substantial number of copy number of alterations. Genomically, colorectal and metastatic liver tumors were very similar. However, in a subgroup of patients, there were genetic variations in liver metastases in the loss of DNA mismatch repair genes. Copy number analysis of Affymetrix CytoScanHD arrays was performed for 15 primary colorectal carcinoma and 15 samples of their matched liver metastases. 15 normal samples prepared from each of the patient was used as the reference for the study. Nexus Copy number 6.1 software was used for somatic copy number alteration analysis.
2014-03-01 | E-GEOD-53799 | biostudies-arrayexpress
Project description:We performed whole exome sequencing and copy number analysis for 15 triplets, each comprising normal colorectal tissue, primary colorectal carcinoma, and its synchronous matched liver metastasis. We analyzed the similarities and differences between primary colorectal carcinoma and matched liver metastases in regards to somatic mutations and somatic copy number alterationss (SCNAs). The genomic profiling demonstrated mutations in APC(73%), KRAS (33%), ARID1A and PIK3CA (6.7%) genes between primary colorectal and metastatic liver tumors. TP53 mutation was observed in 47% of the primary samples and 67% in liver metastatic samples. The grouped pairs, in hierarchical clustering showed similar SCNA patterns, in contrast to the ungrouped pairs. Many mutations (including those of known key cancer driver genes) were shared in the grouped pairs. The ungrouped pairs exhibited distinct mutation patterns with no shared mutations in key driver genes. Four ungrouped liver metastasis samples had mutations in DNA mismatch repair genes along with hypermutations and a substantial number of copy number of alterations. Genomically, colorectal and metastatic liver tumors were very similar. However, in a subgroup of patients, there were genetic variations in liver metastases in the loss of DNA mismatch repair genes.
2014-03-01 | GSE53799 | GEO
Project description:Variable tumor cellularity can limit sensitivity and precision in comparative genomics, because differences in tumor content can result in misclassifying truncal mutations as region-specific private mutations in stroma-rich regions, especially when studying tissue specimens of mediocre tumor cellularity such as LUADs. To address this issue, we refined a nuclei flow-sorting approach by sorting nuclei based on ploidy and the LUAD lineage marker thyroid transcription factor 1 (TTF-1) and applied this method to investigate genome-wide somatic copy number aberrations (SCNA) and mutations of 409 cancer genes in 39 tumor populations obtained from 16 primary tumors and 21 matched metastases. This approach increased the mean tumor purity from 54% (range: 7-89%) of unsorted material to 92% (range: 79-99%) after sorting. Despite this rise in tumor purity, we detected limited genetic heterogeneity between primary tumors and their metastases. In fact, 88% of SCNAs and 80% of mutations were propagated from primary tumors to metastases and low allele frequency mutations accounted for much of the mutational heterogeneity. Even though the presence of SCNAs indicated a history of chromosomal instability (CIN) in all tumors, metastases did not have more SCNAs than primary tumors. Moreover, tumors with biallelic TP53 or ATM mutations had high numbers of SCNAs, yet they were associated with a low interlesional genetic heterogeneity. The results of our study thus provide evidence that most macroevolutionary events occur in primary tumors before metastatic dissemination and advocate for a limited degree of CIN over time and space in this cohort of LUADs. Sampling of primary tumors thus may suffice to detect most mutations and SCNAs. In addition, metastases but not primary tumors had seeded additional metastases in three of four patients; this provides a genomic rational for surgical treatment of such oligometastatic LUADs.
2018-09-11 | GSE119763 | GEO
Project description:NHNP cells (Lonza, Belgium) were grown in Maintenance medium for 24 h. Differentiation was induced by withdrawal of EGFand FGF and addition of BDNF. ArrayCGH experiments were done before differentiation, 24h, 2d and 5d after differentiation induction.
2014-01-01 | GSE30636 | GEO
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
Project description:DNA copy number alterations and mutations were characterised by bulk SNP anlaysis and exome sequencing (not sown here) in three acute lymphoblastic leukaemia samples and one establish cell line REH. Further single cell experiments of these cases investigated the mutation and copy number targets previously defined exploring the sub-clonal populations and phylogenic trees within each leukaemia. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved diagnostic bone marrow or peripheral blood samples.
2013-07-26 | GSE49215 | GEO
Project description:NHNP cells (Lonza, Belgium) were grown in Maintenance medium for 24 h. Differentiation was induced by withdrawal of EGFand FGF and addition of BDNF. ArrayCGH experiments were done before differentiation, 24h, 2d and 5d after differentiation induction. ArrayCGH from undifferentiated NHNP cells, 24h differentiated NHNP cells, 2d differentiated NHNP cells and 5d differentiated NHNP cells
2014-01-01 | E-GEOD-30636 | biostudies-arrayexpress
Project description:The RNA isolated from 60 Neuroendocrine Neoplasm (NEN) was analysed to identify differentially expressed transcripts and fusion transcripts. Library preparation was performed using two different kit: TruSeq Stranded Total RNA (Illumina) for frozen samples and extracted RNAs, and TruSeq RNA Exome (Illumina) for FFPE samples.
2022-06-30 | E-MTAB-11599 | biostudies-arrayexpress