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Affymetrix SNP 6.0 array data for gastric adenocarcinoma and some matched normals

ABSTRACT: 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 The 111 copy number profiles contained in this archive are the previously unpublished portion of our study.

ORGANISM(S): Homo sapiens

PROVIDER: GSE77775 | GEO | 2017/04/15

SECONDARY ACCESSION(S): PRJNA311521

REPOSITORIES: GEO

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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).

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 271 cancer DNAs derived from primary tissues, as well as from DNA obtained from 60 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 SNP 6.0 data from this submission were segmented using CBS. These segmented data were then combined with segmented Affymetrix 250K Sty data for 128 colon, 13 gastric and 74 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).

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Affymetrix SNP 6.0 array data for gastric adenocarcinoma and some matched normals

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