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Gene mutation of transforming growth factor β1 type II receptor in hepatocellular carcinoma
Author(s) -
Furuta Keiko,
Misao Sachiko,
Takahashi Kiyoshi,
Tagaya Tsuneaki,
Fukuzawa Yoshitaka,
Ishikawa Tetsuya,
Yoshioka Kentaro,
Kakumu Shinichi
Publication year - 1999
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19990611)81:6<851::aid-ijc2>3.0.co;2-d
Subject(s) - hepatocellular carcinoma , mutation , cancer research , biology , carcinoma , gene , transforming growth factor , medicine , oncology , genetics
Alteration of transforming growth factor β1 (TGF‐β1) type II receptor (RII) appears to cause unresponsiveness to TGF‐β1 in tumorigenic cells. Defect in the mononucleotide repeat sequence, i.e., poly A region of TGF‐β1RII gene has been reported to be related to replication error‐positive cancer cells. We examined if there is any TGF‐β1RII mutation in a coding microsatellite in hepatocellular carcinoma (HCC). Genomic DNAs were extracted from formalin‐fixed, paraffin‐embedded liver tissues obtained at surgery or autopsy in 3 normal individuals and 96 patients with hepatitis C virus‐induced chronic liver disease; 3 with chronic hepatitis, 20 with liver cirrhosis and 73 with HCC. The DNA was PCR‐amplified at 2 segments of TGF‐β1RII: poly A region which includes the (A) 10 microsatellite sequence, and poly GT region. PCR products were directly sequenced. DNA from normal and patients with chronic liver disease contained the 10 wild‐type adenines but 3 cases with liver cirrhosis in whom there were only 9 adenines within poly A tract. This microdeletion of one A resulted in a frameshift and truncated a predicted length of amino acids. In HCC lesions, the same deletion was noted in 4 cases (25%) of well‐differentiated type, 10 (40%) of moderately differentiated type, 18 (53%) of poorly differentiated type. None of the lesions had mutations within the GT region. Our findings indicate that one adenine deletion of poly A microsatellite tract within TGF‐β1RII is frequently detected in patients with HCC, and the mutation may cause the abrogation of the function of TGF‐β1RII gene. Int. J. Cancer 81:851–853, 1999. © 1999 Wiley‐Liss, Inc.