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KMID : 1034820100060030321
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Molecular & Cellular Toxicology
2010 Volume.6 No. 3 p.321 ~ p.326
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TGFBR2 frameshift mutation in gastric tumors with microsatellite instability
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Song Jae-Hwi
Lee Hwa-Sung
Yoon Jung-Hwan
Kang Young-Hwi
Nam Suk-Woo
Lee Jung-Young
Park Won-Sang
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Abstract
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Microsatellite instability (MSI) is a form of genetic instability present in virtually all tumors from patients with hereditary nonpolyposis colon cancer and a subset of various sporadic tumors, including colorectal and gastric cancers. Transforming growth factor-beta receptor 2 (TGFBR2) mutations in MSI-positive cancer cell lines may partially inactivate TGF-β-induced growth inhibition. The aim of this study was to investigate whether MSI and TGFBR2 gene mutations contribute to the progression from gastric adenoma to cancer in multistep gastric carcinogenesis. MSIs were analyzed using 5 microsatellite markers and a frameshift mutation in poly(A)10 within the TGFBR2 gene in 50 gastric adenomas and 88 gastric cancer specimens. One (2.0%) of 50 gastric adenomas and 22 (25.0%) of 88 gastric cancers were MSI-positive. TGFBR2 frameshift mutations were found in 9 gastric cancers, but not in adenoma. All cases with the TGFBR2 frameshift mutation showed high-frequency MSIs. These results suggest that MSIs may occur in the development of gastric cancers, but not in adenomas less than 2 cm, and the TGFBR2 gene may be a target of genomic instability in MSI gastric carcinogenesis.
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KEYWORD
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TGFBR2, Microsatellite instability, Mutation, Gastric cancers
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