Affymetrix 250K StyI SNP array data across multiple human cancer types
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE19399 | GEO | 2010/02/18
SECONDARY ACCESSION(S): PRJNA121763
REPOSITORIES: GEO
Similar Datasets
Project description:Using data from high-density genomic profiling arrays, we describe the profiles of somatic copy-number aberrations (SCNAs) in 486 adenocarcinomas across all three major digestive organs, including 296 gastric and esophageal cancers. This analysis revealed that although patterns of broad, chromosome arm-level alterations are similar across the three types of adenocarcinoma, focal genomic amplifications are substantially more prevalent in gastric/esophageal adenocarcinoma. A statistical analysis identified 64 regions of significantly recurrent amplification and deletion, including those shared across these tumors and those uniquely significant in adenocarcinomas from a single organ. Among significantly amplified genes are those encoding therapeutically targetable kinases such as ERBB2, FGFR1, FGFR2, EGFR, and MET, events noted in 14% of colorectal adenocarcinomas and 37% of gastric/esophageal tumors suggesting that analysis of genomic amplification will be a critical source of biomarkers to guide therapies in upper gastrointestinal adenocarcinomas. While many of the other significant loci of amplifications implicate genes recognized to play roles in gastrointestinal and other cancers, other loci point to regions that may harbor novel genes contributing to these cancers. One such event is a recurrent focal deletion present in 15% of esophageal adenocarcinomas, which we narrow to a single likely target, the Runt transcription factor subunit RUNX1. Indeed, reintroduction of RUNX1 into a cell model with this deletion inhibited anchorage-independent growth. Overall, these results demonstrate genomic features common to these tumors and identify key differences that reflect distinctive biology and potential opportunities for therapeutic intervention.
2012-09-04 | GSE36459 | GEO
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.
2013-03-16 | GSE45190 | GEO
Project description:Using data from high-density genomic profiling arrays, we describe the profiles of somatic copy-number aberrations (SCNAs) in 486 adenocarcinomas across all three major digestive organs, including 296 gastric and esophageal cancers. This analysis revealed that although patterns of broad, chromosome arm-level alterations are similar across the three types of adenocarcinoma, focal genomic amplifications are substantially more prevalent in gastric/esophageal adenocarcinoma. A statistical analysis identified 64 regions of significantly recurrent amplification and deletion, including those shared across these tumors and those uniquely significant in adenocarcinomas from a single organ. Among significantly amplified genes are those encoding therapeutically targetable kinases such as ERBB2, FGFR1, FGFR2, EGFR, and MET, events noted in 14% of colorectal adenocarcinomas and 37% of gastric/esophageal tumors suggesting that analysis of genomic amplification will be a critical source of biomarkers to guide therapies in upper gastrointestinal adenocarcinomas. While many of the other significant loci of amplifications implicate genes recognized to play roles in gastrointestinal and other cancers, other loci point to regions that may harbor novel genes contributing to these cancers. One such event is a recurrent focal deletion present in 15% of esophageal adenocarcinomas, which we narrow to a single likely target, the Runt transcription factor subunit RUNX1. Indeed, reintroduction of RUNX1 into a cell model with this deletion inhibited anchorage-independent growth. Overall, these results demonstrate genomic features common to these tumors and identify key differences that reflect distinctive biology and potential opportunities for therapeutic intervention. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from 87 cancer DNAs derived from primary tumor tissues, as well as from DNA obtained from 1,480 normal DNA samples. Signal intensities were normalized to raw copy number estimates using the tangent normalization method, as described in Beroukhim et al., In Press and Mermel et al., In preparation. The 250K Sty data from this submission were combined with data for 128 colon adenocarcinomas (Firestein et al, Nature 2008) and segmented using GLAD. These segmented data were then combined with segmented SNP 6.0 data for 62 colon, 97 gastric and 112 esophageal adenocarcinomas using common markers to anchor the segments. Data analysis across samples was performed using this GISTIC 2.0 algorithm (Mermel C et al, Genome Biology 2011).
2012-09-04 | E-GEOD-36459 | biostudies-arrayexpress
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:The landscape of somatic copy-number alterations (SCNAs) affecting long non-coding RNAs (lncRNAs) in human cancer remains largely unexplored. While the majority of lncRNAs remains to be functionally characterized, several have been implicated in cancer development and metastasis. Considering the plethora of lncRNAs genes that is currently reported, it is conceivable that several lncRNAs might function as oncogenes or tumor suppressor genes. We devised a strategy to detect focal lncRNA SCNAs using a custom DNA microarray platform probing 20 418 lncRNA genes. By screening a panel of 80 cancer cell lines, we detected numerous focal aberrations targeting one or multiple lncRNAs without affecting neighboring protein-coding genes. These focal aberrations are highly suggestive for a tumor suppressive or oncogenic role of the targeted lncRNA gene. Although functional validation remains an essential step in the further characterization of the involved candidate cancer lncRNAs, our results provide a direct way of prioritizing candidate lncRNAs involved in cancer pathogenesis.
2017-01-01 | GSE85444 | 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:Genomics has provided a detailed structural description of the cancer genome. Identifying oncogenic drivers that work primarily through dosage changes is a current challenge. Unrestrained proliferation is a critical hallmark of human cancer. We constructed modular, barcoded libraries of human open reading frames (ORFs) and performed screens for proliferation regulators in multiple cell types. Approximately 10% of genes tested regulate proliferation, many performing in an unexpectedly highly tissue-specific manner. Proliferation drivers in a given cell type showed specific enrichment in SCNAs (somatic copy number changes) from cognate tumors and helped predict aneuploidy patterns in those tumors, implying that tissue type-specific genetic network architectures underlie SCNA selection in different cancers. In vivo screening confirmed these results. We report a substantial contribution to the catalog of SCNA-associated cancer drivers, identifying 147 amplified and 107 deleted genes as potential drivers, and derive new insights about the genetic network architecture of aneuploidy in tumors. KRTAPs are a class of human genes that promote proliferation in mammary epithelial cells (HMEC), but the mechanism is not understood. We performed RNAseq to study transcriptional changes associated with oeverxepression of KRTAPs and other oncogenes in hTERT-immortalized human mammary epithelial cells. GSEA analysis revealed the top enriched pathways upregulated by KRTAP expression are E2F-mediated regulation of DNA replication, G1-S specific transcription, cell cycle, translation and ribosome. KRTAP-induced mRNA changes are most closely related to those due to CCND1 expression, including induction of E2F1 transcription factor.
2018-05-01 | GSE109326 | GEO
Project description:Using data from high-density genomic profiling arrays, we investigated the profiles of somatic copy-number aberrations (SCNAs) in 659 gastric adenocarcinomas drawn approximately even numbers of Asian and Western patients with two goals in mind: (1) using the power of our large data set to detect new, and refine existing, regions of significantly recurring SCNAs; (2) determining if there exist fundamental differences in the manifestation of gastric adenocarcinoma in Asian versus Western patients that affect pattern of SCNAs. Among the 83 regions of significant alteration we indeed found some new targets in gastric adenocarcinoma such as the tumor suppressor gene SMARCA4 and proto-oncogene MYB, and additionally refined the boundaries of known significant regions. We found only slight differences in the overall copy number patterns between Asian and Western gastric adenocarcinoma patients indicating that the disease is fundamentally similar in both populations and the divergent clinical outcomes cannot be ascribed to different underlying SCNAs. The 111 copy number profiles contained in this archive are the previously unpublished portion of our study.
2017-04-15 | GSE77775 | GEO
Project description:Metastatic colorectal cancer (mCRC) is associated with multiple somatic copy number alterations (SCNAs). We analyzed SCNAs to estimate overall survival (OS) and progression free suvival (PFS) for mCRC patients treated with bevacizumab in combination with oxaliplatin or irinotecan.
2018-11-21 | GSE110785 | GEO
Project description:Medulloblastoma, the most common malignant pediatric brain tumour is currently treated with non-specific cytotoxic therapies including surgery, whole brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, prior attempts to identify targets for therapy have been underpowered due to small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1087 unique medulloblastomas. SCNAs are more common than SNVs in medulloblastoma, and are predominantly subgroup enriched. The most common region of focal copy number gain is a tandem duplication of the Parkinson's disease gene SNCAIP, which is exquisitely restricted to Subgroup 4alpha. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1 that arise through localized chromosomal shattering (topochromothripsis) are restricted to Group 3 tumours. Numerous actionable SCNAs, including recurrent events targeting TGFbeta signaling in Group 3, and NF-kappaB signaling in Group 4 suggest future avenues for rational, targeted therapy This SuperSeries is composed of the SubSeries listed below.
2012-07-27 | GSE37385 | GEO