Open AccessPTEN/MMAC1 Mutations in Hepatocellular Carcinomas: Somatic Inactivation of Both Alleles in Tumors
Author(s) -
Kawamura Naoki,
Nagai Hisaki,
Bando Koichi,
Koyama Masaaki,
Matsumoto Satoshi,
Tajiri Takashi,
Onda Masahiko,
Fujimoto Jiro,
Ueki Takahiro,
Konishi Noboru,
Shiba Tadayoshi,
Emi Mitsuru
Publication year - 1999
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1999.tb00763.x
Subject(s) - biology , loss of heterozygosity , missense mutation , pten , exon , frameshift mutation , allele , genetics , point mutation , cancer research , germline mutation , locus (genetics) , mutation , gene , microbiology and biotechnology , apoptosis , pi3k/akt/mtor pathway
Allelic loss of loci on chromosome 10q occurs frequently in hepatocellular carcinomas. Somatic mutations of the PTEN/MMAC1 gene on this chromosome at 10q23 were recently identified in sporadic cancers of the uterus, brain, prostate and breast. To investigate the potential role of PTEN/MMAC1 gene in the genesis of hepatocellular carcinomas, we examined 96 tumors for allelic loss on 10q and also for subtle mutations anywhere within the coding region of PTEN/MMAC1 gene. Allelic loss was identified in 25 of the 89 (27%) tumors that were informative for polymorphic markers in the region. Somatic mutations were identified in five of those tumors: three frameshift mutations, a 1‐bp insertion at codon 83–84 in exon 4 and two 4‐bp deletions, both at codon 318–319 in exon 8; two C‐to‐G transversion mutation, both at ‐9 bp from the initiation codon in the 5’non‐coding region of exon 1. No missense mutation was observed in this panel of tumors. In most of the informative tumors carrying intragenic mutations of one allele, we were able to detect loss of heterozygosity as well. These findings suggest that two alleles of the PTEN/MMAC1 gene may be inactivated by a combination of intragenic point mutation on one allele and loss of chromosomal material on the other allele in some of these tumors.