Loss of heterozygosity suggests tumor suppressor gene responsible for primary hepatocellular carcinoma

K H Buetow; J C Murray; J L Israel; W T London; M Smith; M Kew; V Blanquet; C Brechot; A Redeker; S Govindarajah

doi:10.1073/pnas.86.22.8852

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Loss of heterozygosity suggests tumor suppressor gene responsible for primary hepatocellular carcinoma

Journal article

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Loss of heterozygosity suggests tumor suppressor gene responsible for primary hepatocellular carcinoma

K H Buetow, J C Murray, J L Israel, W T London, M Smith, M Kew, V Blanquet, C Brechot, A Redeker and S Govindarajah

Proceedings of the National Academy of Sciences - PNAS, Vol.86(22), pp.8852-8856

11/1989

DOI: 10.1073/pnas.86.22.8852

PMCID: PMC298388

PMID: 2573067

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Abstract

Primary hepatocellular carcinoma (PHC), epidemiologically associated with chronic hepatitis B virus (HBV) infection, has historically been felt to be caused by the activation or introduction of an oncogene. However, transforming sequences from human PHC have not been reproducibly isolated. In this paper, evidence is presented that suggests PHC may result instead from the loss of an anti-oncogene. Seven of 12 human primary liver tumors tested against a panel of restriction fragment length polymorphisms (RFLPs) demonstrated loss of constitutional heterozygosity for markers on chromosome 4. Tumor and nontumor liver tissue were typed for 11 chromosome 4 RFLPs. In addition, at least one RFLP on nine other chromosomes (1, 2, 6, 7, 9, 11, 13, 14, and 17) was tested for allelic loss. Seven of nine tumors constitutionally heterozygous for chromosome 4q markers showed allele loss in tumor tissue. Six of the seven samples were jointly informative for both 4p and 4q markers. Five of the six demonstrated loss for only 4q RFLPs. In one individual, in which two samples were taken from distant locations within the same tumor, both samples showed loss of the same alleles. Among the other chromosomes informative for allele loss, one tumor showed changes on 13q. No other changes were observed in RFLPs located on the eight other chromosomes tested. These results indicate that an anti-oncogene may be located on 4q and suggest a mechanism for PHC and other cancers seroepidemiologically related to virus infection. Liver cancer caused by chronic HBV infection or other environmental agents may be linked through genetic events responsible for the loss of a tumor suppressor locus (anti-oncogene) located on chromosome 4.

Details

Title: Subtitle: Loss of heterozygosity suggests tumor suppressor gene responsible for primary hepatocellular carcinoma
Creators: K H Buetow - Fox Chase Cancer Center, Philadelphia, PA 19111
J C Murray - University of Iowa
J L Israel - Fox Chase Cancer Center, Philadelphia, PA 19111
W T London - Fox Chase Cancer Center, Philadelphia, PA 19111
M Smith - University of California, Irvine
M Kew - University of the Witwatersrand
V Blanquet - Institut Pasteur
C Brechot - Institut Pasteur
A Redeker - Rancho Los Amigos National Rehabilitation Center
S Govindarajah - Rancho Los Amigos National Rehabilitation Center
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.86(22), pp.8852-8856
DOI: 10.1073/pnas.86.22.8852
PMID: 2573067
PMCID: PMC298388
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences
Language: English
Date published: 11/1989
Academic Unit: Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research
Record Identifier: 9984025406602771

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