Molecular pathobiology of gastric cancer.
Gastric carcinogenesis is a multistep process, during which numerous genetic and epigenetic alterations accumulate: there are abnormalities of growth factors/receptors, angiogenic factors, cell cycle regulators, DNA mismatch repair genes etc. These abnormalities define, at the same time, the biological character of the cancer cell and may thus serve as therapeutic targets. Genetic instability may cause accumulation of genetic abnormalities. The most important epigenetic alterations are DNA methylation, histone modification and chromatin remodeling. Some of these changes are common in gastric cancer, regardless of subtype, and some differ by histological type or (gastric or intestinal) mucin phenotype. Genetic polymorphism is a crucial endogenous cause and fundamental aspect of cancer risk. Importantly, genetic polymorphisms are also associated with the therapeutic efficacy and toxicity of anti-cancer drugs. Genomic science and technology such as Serial Analysis of Gene Expression (SAGE) allows the identification of novel genes and molecules specifically up-regulated or down-regulated in gastric cancer, e.g., RegIV and claudin-18 can be identified. Advances in our understanding of the genetic and molecular bases lead to improved diagnosis, personalised medicine and prevention of gastric cancer.
Yasui
W
W
Department of Molecular Pathology, Hiroshima University Graduate School of Biomedical Sciences, Minami-ku, Hiroshima, Japan. wyasui@hiroshima-u.ac.jp
Sentani
K
K
Motoshita
J
J
Nakayama
H
H
D018797:Cell Cycle Proteins / Q000235:genetics; D044127:Epigenesis, Genetic; D015870:Gene Expression; D042822:Genomic Instability; D016481:Helicobacter Infections; D016480:Helicobacter pylori / Q000472:pathogenicity; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D011110:Polymorphism, Genetic; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000235:genetics* / Q000382:microbiology
D018797:Cell Cycle Proteins; D036341:Intercellular Signaling Peptides and Proteins