Genetic aberration in primary hepatocellular carcinoma: correlation between p53 gene mutation and loss-of-heterozygosity on chromosome 16q21-q23 and 9p21-p23.
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.
Wang
G
G
National Laboratory for Oncogene and Related Genes, Shanghai Cancer Institute, China.
Huang
C H
CH
Zhao
Y
Y
Cai
L
L
Wang
Y
Y
Xiu
S J
SJ
Jiang
Z W
ZW
Yang
S
S
Zhao
T
T
Huang
W
W
Gu
J R
JR
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
D015820:Cadherins