INFREQUENT POINT MUTATIONS IN CODON-12 AND CODON-61 OF RAS ONCOGENES IN HUMAN HEPATOCELLULAR CARCINOMAS

C CHALLEN, K GUO, J D COLLIER, D CAVANAGH, M F BASSENDINE

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

DNA from human hepatocellular carcinomas (HCC) were analysed for the presence of mutations in codons 12 and 61 of the K-ras, H-ras and N-ras genes. The relevant ras sequences were amplified in vitro using the polymerase chain reaction and point mutations detected by selective hybridisation using mutation-specific synthetic oligonucleotides. In one of the 19 HCCs a mutation in codon 61 of the K-ras gene was detected, whilst in 3/19 HCCs a mutation was found in codon 61 of the N-ras gene. The mutations were all heterozygous A-T transversions and were found in HCCs arising in patients with underlying cirrhosis. In two of these patients where the corresponding normal tissue was available only the wild-type ras gene was detected, indicating that oncogenic activation of the ras gene was a consequence of somatic mutation. In another patient the same mutation in codon 61 of the N-ras gene was found in cirrhotic liver tissue and in all four patients the same mutation was also detected in formalin-fixed, paraffin-embedded liver biopsy HCC tissue obtained at diagnosis. These results indicate that mutational activation of the ras genes at codon 61 is an infrequent but possibly early event in the development of HCC in Britain.

Original languageEnglish
Pages (from-to)342-346
Number of pages5
JournalJournal of Hepatology
Volume14
Issue number2-3
Publication statusPublished - Mar 1992

Keywords / Materials (for Non-textual outputs)

  • C-HA-RAS
  • POLYMERASE CHAIN-REACTION
  • MOUSE-LIVER TUMORS
  • KI-RAS
  • B6C3F1 MOUSE
  • ACTIVATING MUTATIONS
  • MYC GENES
  • CARCINOGENESIS
  • EXPRESSION
  • HEPATOCARCINOGENESIS

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