Mutation at codon 249 of p53 gene in a human hepatoblastoma

✍ Scribed by Siddhartha Kar; Ron Jaffe; Dr. Brian I. Carr

• Publisher: John Wiley and Sons
• Year: 1993
• Tongue: English
• Weight: 403 KB
• Volume: 18
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840180314

✦ Synopsis

G-to-T transversion at codon 249 of the p53 gene has been shown to be specifically associated with human hepatocellular carcinomas, particularly that subset associated with exposure to the chemical hepatocarcinogen aflatoxin B,. We surveyed 47 North American adult hepatocellular carcinomas and three childhood liver tumors for codon 249 mutation. W e report here a case of childhood hepatoblastoma in a patient, without known exposure to aflatoxin B, or hepatitis B or C virus, whose tumor had a mutation at codon 249 involving G-to-T transversion. (HEPATOLOGY 1993; 18: 566-569.)

Mutations involving the tumor-suppressor gene p53 have been found in many human primary tumors (1). Several mutation hot spots have also been identified in this gene. A specific mutation in the third base of codon 249, involving G-to-T or G-to-C transversion, has been specifically associated with a subset of human HCCs from China and South Africa thought to be associated with aflatoxin B, exposure (2-4). However, considerable variability exists in the literature with regard to the association of primary liver cancer and aflatoxin B, exposure (51, and some aflatoxin B,-induced HCCs from nonhuman primates do not contain the codon 249 mutation (6). We therefore surveyed our collection of North American HCCs and some hepatoblastomas. We report here our finding of no codon 249 mutations in any of 47 North American HCCs. However, in one of three childhood hepatoblastomas surveyed we found a G-to-T transversion at codon 249. To our knowledge, this is the first report of the association of this mutation with hepatoblastoma. We found no evidence of aflatoxin B, or HBV exposure in this child.

Methods

RNA was extracted from tumor and surrounding tissues with RNAZol (Cinna-Biotex Lab, Friendswood, TX). The RNA was subjected to reverse-transcription (RT), and the comple-