Genomic profile analysis of diffuse-type gastric cancers
Cited 12 times inCited 12 times in
- Genomic profile analysis of diffuse-type gastric cancers
- Lee, Yeon-Su; Cho, Yun Sung; Lee, Geon Kook; Lee, Sunghoon; Kim, Young-Woo; Jho, Sungwoong; Kim, Hak-Min; Hong, Seung-Hyun; Hwang, Jung-Ah; Kim, Sook-young; Hong, Dongwan; Choi, Il Ju; Kim, Byung Chul; Kim, Byoung-Chul; Kim, Chul Hong; Choi, Hansol; Kim, Youngju; Kim, Kyung Wook; Kong, Gu; Kim, Hyung Lae; Bhak, Jong Hwa; Lee, Seung Hoon; Lee, Jin Soo
- E-CADHERIN GENE; AMINO-ACID SUBSTITUTIONS; SOMATIC MUTATIONS; FUNCTIONAL INACTIVATION; LUNG ADENOCARCINOMA; SEQUENCING DATA; CELL-ADHESION; UNITED-STATES; CARCINOMA; LANDSCAPE
- Issue Date
- BIOMED CENTRAL LTD
- GENOME BIOLOGY, v.15, no.4, pp.1 - 15
- 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.
- ; Go to Link
- Appears in Collections:
- BME_Journal Papers
- Files in This Item:
can give you direct access to the published full text of this article. (UNISTARs only)
Show full item record
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.