A majority of liver cancer patients from China and Africa havemutations clustered at one site in the p53 tumor suppressorgene.

This clustering suggests that the site is a "hot spot" formutations caused by agents that trigger cancer development.Both the hepatitis B virus (HBV) and aflatoxin, a carcinogenfound in nuts, are linked to liver cancer in China and Africa.Exposure to either HBV or aflatoxin leads to liver cancer inanimal models.

Two independent research groups report this hot spot p53mutation site in today's Nature. Curtis C. Harris of the NationalCancer Institute and his colleagues showed that eight of 16Chinese liver cancer patients had a point mutation at the thirdnucleotide of p53's codon 249. (A codon is a three-nucleotidesequence that encodes an amino acid.)

Mehmet Ozturk from Massachusetts General Hospital and hiscolleagues reported that three of 10 African liver cancerpatients had the same mutation at codon 249. Two otherpatients had single point mutations in different codons.

In each case, a guanosine was replaced by either a thymidineor cytosine. Both groups said that the nature of the pointmutations suggested that they were caused by aflatoxin.

The clustering of mutations to a hot spot is not found in othercancers. For example, the p53 mutations found in breast, lung,colon and bladder tumors are scattered throughout severalregions of the gene.

Identification of mutations leading to p53's inability tosuppress tumor formation may lead to an understanding of themechanisms by which carcinogens and viruses cause cancer.Several companies, including Applied bioTechnology Inc., F.Hoffmann-La Roche & Co., Oncogene Science Inc., Oncor Inc. andViagene Inc., are developing diagnostics and therapeutics basedon tumor suppressor genes and oncogenes.

-- Carol Talkington Verser, Ph.D. Special to BioWorld

(c) 1997 American Health Consultants. All rights reserved.

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