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Genetic alterations of the HCCS1 gene in Korean hepatocellular carcinoma

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Abstract:

Xiao W, Park CK, Park JY, Lee JH, Kim HS, Cho YG, Kim CJ, AhnYM, Lee JH, Song YH, Lee SH, Yoo NJ, Lee JY, Park WS. Genetic alterations of the HCCS1 gene in Korean hepatocellular carcinoma. APMIS 2003;111:465–73.

We analyzed the gene mutations and loss of heterozygosity (LOH) of the HCCS1 gene using intragenic polymorphic markers in a series of 88 primary HCCs. We found two sequence variations at exon 5 and 14 in both normal and tumor DNAs of case 50 and 51, respectively. The variation in case 50 led to a reading frameshift and a premature stop (TGA) at codon 125 and case 51 showed amino acid change at codon 448 (Val→Ala, G TG→G CG). Interestingly, these variations were not found in peripheral lymphocytes of 69 normal individuals and 227 cancer patients (86 HCC, 75 unselected gastric cancer, and 66 breast cancer), suggesting that these two variations are mutation, not polymorphism. In addition, we found 14 novel intragenic polymorphic sites in the HCCS1 gene. Thirty-two (47%) of sixty-eight informative cases showed allelic loss at at least one or more intragenic polymorphic sites, but there was no significant relationship between the frequency of LOH and clinicopathologic parameters. These results suggest that mutation of the HCCS1 gene might not be a main inactivation mechanism in the development of Korean HCC and that the HCCS1 gene might be involved in acceleration of the tumorigenic process in Korean HCC.

Keywords: Hepatocellular carcinoma; loss of heterozygosity; mutation; polymorphism

Document Type: Research Article

Affiliations: 1: Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul, Korea 2: Department of Diagnostic Pathology, Samsung Medical Center, School of Medicine, Sungkunkwan University, Seoul, Korea 3: Department of the Kidney System, College of Oriental Medicine, Kyung Hee University, Seoul, Korea

Publication date: April 1, 2003

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