title: Genetic aberration in primary hepatocellular carcinoma: correlation between p53 gene mutation and loss-of-heterozygosity on chromosome 16q21-q23 and 9p21-p23.
abstract: 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.
authors.affiliation: National Laboratory for Oncogene and Related Genes, Shanghai Cancer Institute, China.
authors.forename: G
authors.initials: G
authors.lastname: Wang
authors.forename: C H
authors.initials: CH
authors.lastname: Huang
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.forename: L
authors.initials: L
authors.lastname: Cai
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: S J
authors.initials: SJ
authors.lastname: Xiu
authors.forename: Z W
authors.initials: ZW
authors.lastname: Jiang
authors.forename: S
authors.initials: S
authors.lastname: Yang
authors.forename: T
authors.initials: T
authors.lastname: Zhao
authors.forename: W
authors.initials: W
authors.lastname: Huang
authors.forename: J R
authors.initials: JR
authors.lastname: Gu
mesh_terms: D015820:Cadherins / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000235:genetics*; D002681:China; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D017353:Gene Deletion; D019942:Genes, p16 / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology / Q000235:genetics*; D019656:Loss of Heterozygosity / Q000235:genetics*; D018895:Microsatellite Repeats / Q000235:genetics; D009154:Mutation
chemical_list: D015820:Cadherins