Abstract
Background Gastric cancer, a leading cause of cancer death worldwide, has been little studied compared with other cancers that impose similar health burdens. Our goal is to assess genomic copy-number loss and the possible functional consequences and therapeutic implications thereof across a large series of gastric adenocarcinomas. Methods We used high-density single-nucleotide polymorphism microarrays to determine patterns of copy-number loss and allelic imbalance in 74 gastric adenocarcinomas. We investigated whether suppressor of tumorigenesis and/or proliferation (STOP) genes are associated with genomic copy-number loss. We also analyzed the extent to which copy-number loss affects Copy-number alterations Yielding Cancer Liabilities Owing to Partial losS (CYCLOPS) genes–genes that may be attractive targets for therapeutic inhibition when partially deleted.ResultsThe proportion of the genome subject to copy-number loss varies considerably from tumor to tumor, with a median of 5.5 %, and a mean of 12 % (range 0–58.5 %). On average, 91 STOP genes were subject to copy-number loss per tumor (median 35, range 0–452), and STOP genes tended to have lower copy-number compared with the rest of the genes. Furthermore, on average, 1.6 CYCLOPS genes per tumor were both subject to copy-number loss and downregulated, and 51.4 % of the tumors had at least one such gene.ConclusionsThe enrichment of STOP genes in regions of copy-number loss indicates that their deletion may contribute to gastric carcinogenesis. Furthermore, the presence of several deleted and downregulated CYCLOPS genes in some tumors suggests potential therapeutic targets in these tumors.Electronic supplementary materialThe online version of this article (doi:10.1007/s10120-015-0514-z) contains supplementary material, which is available to authorized users.
Highlights
Gastric cancer is the fourth commonest cancer in the world and a leading cause of cancer death [1]
We found that Genome Alteration Print (GAP) was often unable to detect allelic imbalance from the B-allele frequencies (BAFs) data (Fig. S1)
We believe that very low proportions of malignant cells in the tumor samples were responsible for the BAFs that were uniformly 0.5, for the reasons described in the caption for Fig. S6
Summary
Gastric cancer is the fourth commonest cancer in the world and a leading cause of cancer death [1]. High-density microarrays provide simultaneous assessment of single-nucleotide polymorphism (SNP) genotype and genomic copy number at hundreds of thousands of sites across the genome, and can delineate regions of copynumber loss [10]. A leading cause of cancer death worldwide, has been little studied compared with other cancers that impose similar health burdens. Our goal is to assess genomic copy-number loss and the possible functional consequences and therapeutic implications thereof across a large series of gastric adenocarcinomas. Methods We used high-density single-nucleotide polymorphism microarrays to determine patterns of copynumber loss and allelic imbalance in 74 gastric adenocarcinomas.
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