gastric adenocarcinoma
Gastric cancer is thought to result from a combination of environmental factors and the accumulation of specific genetic alterations due to increasing genetic instability, and consequently affects mainly older patients.
Early onset
Less than 10% of patients present with the disease before 45 years of age (early onset gastric carcinoma) and these patients are believed to develop gastric carcinomas with a molecular genetic profile differing from that of sporadic carcinomas occurring at a later age. In young patients, the role of genetics is presumably greater than in older patients, with less of an impact from environmental carcinogens.
As a result, hereditary gastric cancers and early onset gastric cancers can provide vital information about molecular genetic pathways in sporadic cancers and may aid in the unraveling of gastric carcinogenesis.
Predisposition
Helicobacter infection
Genetic predisposition
10% of familial clustering
E-cadherin gene (CDH1) mutations
mismatch repair genes mutations
- MSH2
- MLH1
germline P53 mutations (Li-Fraumeni syndrome)
Joined CNA-gene expression profiling study
tumor suppressors or deleted in various tumors
- GATA binding protein 4 (GATA4)
- monoamine oxidase A (MAOA)
- cyclin C (CCNC)
oncogenes
- malignant fibrous histiocytoma amplified sequence 1 (MFHAS1/MASL1)
- high mobility group AT-hook 2 (HMGA2)
- PPAR binding protein (PPARBP)
- growth factor receptor-bound protein 7 (GRB7)
- TBC1 (tre-2, BUB2, cdc16) domain family member 1 (TBC1D1)
CGH (15623941)
gains
- 1q gain
- 1q21 gain
- 1q32.3 gain
- 8p23.1-p23.3 gain
- 8q24.2 gain
- 8q24.1 gain
- 7p11.2 gain
- 10p gain
- 20q gain (20q11 gain, 20q13)
- 20q13.12 gain
- 20q13.2 gain
losses
- 1p loss
- 5p loss
- 5q14.1 loss
- 9p21.3-p24.3 loss
- 13q31.1 loss
- 16q22.1 loss
- 17p13.1-p13.3 loss
- 18q22.1 loss
- 19p13.12-p13.3 loss
- 21q21.3 loss
regional amplifications
- 7q21-q22 amplification
- 12q14.1-q21.1 amplification
Videos
Endoscopy of a gastric carcinoma (stomach cancer)
Endoscopy of a small gastric carcinoma (stomach cancer)
References
Milne AN, Sitarz R, Carvalho R, Carneiro F, Offerhaus GJ. Early onset gastric cancer: on the road to unraveling gastric carcinogenesis. Curr Mol Med. 2007 Feb;7(1):15-28. PMID: 17311530
Yang S, Jeung HC, Jeong HJ, Choi YH, Kim JE, Jung JJ, Rha SY, Yang WI, Chung HC. Identification of genes with correlated patterns of variations in DNA copy number and gene expression level in gastric cancer. Genomics. 2007 Jan 15; PMID: 17229543
Tahara E. Genetic pathways of two types of gastric cancer. IARC Sci Publ. 2004;(157):327-49. PMID: 15055305
Simpson AJ, Caballero OL, Pena SD. Microsatellite instability as a tool for the classification of gastric cancer. Trends Mol Med. 2001 Feb;7(2):76-80. PMID: 11286759
Weiss MM, Kuipers EJ, Postma C, Snijders AM, Pinkel D, Meuwissen SG, Albertson D, Meijer GA. Genomic alterations in primary gastric adenocarcinomas correlate with clinicopathological characteristics and survival. Cell Oncol. 2004;26(5-6):307-17. PMID: 15623941