Genetic aberration in primary hepatocellular carcinoma: correlation between p53 gene mutation and loss-of-hetero- zygosity on chromosome 16q21-q23 and 9p21-p23

WANG Gang^1,2, Chang Hui HUANG², Yan ZHAO², Ling CAI², Ying WANG², Shi Jin XIU², Zheng Wen JIANG², Shuang YANG², Xin Tai ZHAO¹, Wei HUANG², Jian Ren GU^1,*

¹National Laboratory for Oncogene and Related Genes, Shanghai Cancer Institute, 25/2200, Xie-tu Rd, Shanghai 200032, China
²Chinese Human Genome Center at Shanghai, 351 Guo Shou Jin Road, Zhangjiang High Tech Park, Shanghai 201203, China

To elucidate the molecular pathology underlying the development of hepatocellular carcinoma (HCC), we used 41 highly polymorphic microsatellite markers to examine 55 HCC and corresponding non-tumor liver tissues on chromosome 9, 16 and 17. Loss-of-heterozygosity (LOH) is observed with high frequency on chromosomal region 17p13 (36/55, 65 %), 9p21-p23 (28/55, 51 %), 16q21-q23 (27/55, 49 %) in tumors. Meanwhile, microsatellite instability is rarely found in these microsatellite loci. Direct sequencing was performed to detect the tentative mutation of tumor suppressor genes in these regions: p53, MTS1/p16, and CDH1/E-cadherin. Within exon 5-9 of p53 gene, 14 out of 55 HCC specimens (24 %) have somatic mutations, and nucleotide deletion of this gene is reported in HCC for the first time. Mutation in MTS1/p16 is found only in one tumor case. We do not find mutations in CDH1/E-cadherin. Furthermore, a statistically significant correlation is present between p53 gene mutation and loss of chromosome region 16q21-q23 and 9p21-p23, which indicates that synergism between p53 inactivation and deletion of 16q21-q23 and 9p21-p23 may play a role in the pathogenesis of HCC.

Key words: Hepatocellular carcinoma; p53 gene mutation; loss of heterozygosity (LOH); microsatellite marker.