title: Genomic profile analysis of diffuse-type gastric cancers.
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.
authors.forename: Yeon-Su
authors.initials: YS
authors.lastname: Lee
authors.forename: Yun Sung
authors.initials: YS
authors.lastname: Cho
authors.forename: Geon Kook
authors.initials: GK
authors.lastname: Lee
authors.forename: Sunghoon
authors.initials: S
authors.lastname: Lee
authors.forename: Young-Woo
authors.initials: YW
authors.lastname: Kim
authors.forename: Sungwoong
authors.initials: S
authors.lastname: Jho
authors.forename: Hak-Min
authors.initials: HM
authors.lastname: Kim
authors.forename: Seung-Hyun
authors.initials: SH
authors.lastname: Hong
authors.forename: Jung-Ah
authors.initials: JA
authors.lastname: Hwang
authors.forename: Sook-young
authors.initials: SY
authors.lastname: Kim
authors.forename: Dongwan
authors.initials: D
authors.lastname: Hong
authors.forename: Il Ju
authors.initials: IJ
authors.lastname: Choi
authors.forename: Byung Chul
authors.initials: BC
authors.lastname: Kim
authors.forename: Byoung-Chul
authors.initials: BC
authors.lastname: Kim
authors.forename: Chul Hong
authors.initials: CH
authors.lastname: Kim
authors.forename: Hansol
authors.initials: H
authors.lastname: Choi
authors.forename: Youngju
authors.initials: Y
authors.lastname: Kim
authors.forename: Kyung Wook
authors.initials: KW
authors.lastname: Kim
authors.forename: Gu
authors.initials: G
authors.lastname: Kong
authors.forename: Hyung Lae
authors.initials: HL
authors.lastname: Kim
authors.forename: Jong
authors.initials: J
authors.lastname: Bhak
authors.forename: Seung Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: Jin Soo
authors.initials: JS
authors.lastname: Lee
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D015703:Antigens, CD; D015820:Cadherins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D005784:Gene Amplification; D050939:Gene Fusion; D015894:Genome, Human; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000235:genetics*; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000235:genetics
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; C000624653:TSC2 protein, human; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; C458527:RNF216 protein, human; D044767:Ubiquitin-Protein Ligases