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Open Access Highly Accessed Research

Genomic profile analysis of diffuse-type gastric cancers

Yeon-Su Lee1, Yun Sung Cho2, Geon Kook Lee3, Sunghoon Lee2, Young-Woo Kim4, Sungwoong Jho2, Hak-Min Kim2, Seung-Hyun Hong1, Jung-Ah Hwang1, Sook-young Kim1, Dongwan Hong1, Il Ju Choi4, Byung Chul Kim25, Byoung-Chul Kim2, Chul Hong Kim5, Hansol Choi2, Youngju Kim3, Kyung Wook Kim3, Gu Kong6, Hyung Lae Kim7, Jong Bhak2589*, Seung Hoon Lee10* and Jin Soo Lee10

Author Affiliations

1 Cancer Genomics Branch, Research Institute, National Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea

2 Personal Genomics Institute, Genome Research Foundation, 443-270 Suwon, Republic of Korea

3 Department of Pathology and Tumor Tissue Bank, National Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea

4 Gastric Cancer Branch, Research Institute and Hospital, National Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea

5 Theragen BiO Institute, TheragenEtex, 443-270 Suwon, Republic of Korea

6 Department of Pathology, College of Medicine, Hanyang University, Seoul, Republic of Korea

7 Department of Biochemistry, School of Medicine, Ewha Womans University, Seoul, Republic of Korea

8 Program in Nano Science and Technology, Department of Transdisciplinary Studies, Seoul National University, Suwon 443-270, Republic of Korea

9 Advanced Institutes of Convergence Technology Nano Science and Technology, Suwon 443-270, Republic of Korea

10 Research Institute and Hospital, National Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea

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Genome Biology 2014, 15:R55  doi:10.1186/gb-2014-15-4-r55

Published: 1 April 2014

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.