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Point mutation, allelic loss and increased methylation of c‐Ha‐ Ras gene in human hepatocellular carcinoma
Author(s) -
Ogata Norio,
Kamimura Tomoteru,
Asakura Hitoshi
Publication year - 1991
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840130106
Subject(s) - hpaii , hepatocellular carcinoma , loss of heterozygosity , biology , locus (genetics) , microbiology and biotechnology , somatic cell , carcinoma , gene , point mutation , restriction enzyme , dna methylation , allele , cancer research , mutation , genetics , gene expression
Somatic alterations of the c‐Ha‐ ras gene were examined in 21 Japanese patients with hepatocellular carcinoma. Restriction endonuclease analysis by double digestion with Msp I and Hpa II revealed that DNAs from two of 21 hepatocellular carcinoma tissues were affected by nucleotide substitution at the twelfth amino acid coding sequence of the c‐Ha‐ ras gene. DNAs from cirrhotic noncancerous liver tissue, but not leukocytes, of one of these patients possessed the mutation, whereas DNAs from noncirrhotic liver tissue and leukocytes of the other patient did not. In one of the nine patients harboring heterozygosity for c‐Ha‐ ras —related Bam HI‐fragments, the loss of one allele was demonstrated as a somatic change not only in DNA from the tumor tissue but also in DNA from the cirrhotic nontumorous tissue. In two of the 19 patients comparatively examined for digestion patterns of c‐Ha‐ ras locus with Hpa II and Msp I, extensive methylation was observed as a somatic modification in both DNAs from the tumor and the cirrhotic nontumorous tissues. These results thus indicate that the genetic lesions affecting the c‐Ha‐ ras gene do occur in human hepatocellular carcinoma and probably serve as one of the multiple steps in the process of hepatic carcinogenesis. (H EPATOLOGY 1991; 13:31–37).