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Genomic profile analysis of diffuse-type gastric cancers

Title
Genomic profile analysis of diffuse-type gastric cancers
Authors
Lee, Yeon-SuCho, Yun SungLee, Geon KookLee, SunghoonKim, Young-WooJho, SungwoongKim, Hak-MinHong, Seung-HyunHwang, Jung-AhKim, Sook-youngHong, DongwanChoi, Il JuKim, Byung ChulKim, Byoung-ChulKim, Chul HongChoi, HansolKim, YoungjuKim, Kyung WookKong, GuKim, Hyung LaeBhak, JongLee, Seung HoonLee, Jin Soo
Ewha Authors
김형래
SCOPUS Author ID
김형래scopus
Issue Date
2014
Journal Title
GENOME BIOLOGY
ISSN
1465-6906JCR Link1474-760XJCR Link
Citation
vol. 15, no. 4
Publisher
BIOMED CENTRAL LTD
Indexed
SCI; SCIE; SCOPUS WOS
Abstract
Background: Stomach cancer is the third deadliest among all cancers worldwide. Although incidence of the intestinal-type gastric cancer has decreased, the incidence of diffuse-type is still increasing and its progression is notoriously aggressive. There is insufficient information on genome variations of diffuse-type gastric cancer because its cells are usually mixed with normal cells, and this low cellularity has made it difficult to analyze the genome. Results: We analyze whole genomes and corresponding exomes of diffuse-type gastric cancer, using matched tumor and normal samples from 14 diffuse-type and five intestinal-type gastric cancer patients. Somatic variations found in the diffuse-type gastric cancer are compared to those of the intestinal-type and to previously reported variants. We determine the average exonic somatic mutation rate of the two types. We find associated candidate driver genes, and identify seven novel somatic mutations in CDH1, which is a well-known gastric cancer-associated gene. Three-dimensional structure analysis of the mutated E-cadherin protein suggests that these new somatic mutations could cause significant functional perturbations of critical calcium-binding sites in the EC1-2 junction. Chromosomal instability analysis shows that the MDM2 gene is amplified. After thorough structural analysis, a novel fusion gene TSC2-RNF216 is identified, which may simultaneously disrupt tumor-suppressive pathways and activate tumorigenesis. Conclusions: We report the genomic profile of diffuse-type gastric cancers including new somatic variations, a novel fusion gene, and amplification and deletion of certain chromosomal regions that contain oncogenes and tumor suppressors.
DOI
10.1186/gb-2014-15-4-r55
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의학전문대학원 > 의학과 > Journal papers
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