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Hepatitis B virus as an insertional mutagene in a human hepatocellular carcinoma.
Mol Biol Med. 1990 Jun; 7(3):213-22.MB

Abstract

Chronic hepatitis B virus (HBV) infection is etiologically related to human hepatocellular carcinoma (HCC). Most HCCs contain integrated HBV DNA in the liver cellular DNA, suggesting that the integration may be involved in carcinogenesis. From a comparison of a single HBV integration site present in a hepatoma with the corresponding unoccupied site in the non-tumourous tissue of the same liver, we have shown that HBV DNA inserted in a putative cellular exon with striking similarity to the DNA-binding domain of the thyroid/steroid hormone receptors. The corresponding cDNA has been isolated (hap gene) and shown to encode the retinoic acid receptor. In the original patient, integration took place so that the first codons of the viral surface protein gene became fused in frame with most of the hap gene. Because retinoic acid is known to regulate the transcription of target genes crucial for cellular growth and differentiation, it is most probable that consequent to the HBV insertion, hap, usually transcribed at a very low level in normal hepatocytes, became inappropriately expressed as an altered chimaeric retinoic acid receptor, thus contributing to the cell transformation. These results strongly support the possibility that HBV may play a direct role in liver carcinogenesis by insertional mutagenesis.

Authors+Show Affiliations

Unité de Recombinaison et Expression Génétique (INSERM U.163, CNRS UA 271), Institut Pasteur, Paris, France.No affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

2170809

Citation

Dejean, A, and H de Thé. "Hepatitis B Virus as an Insertional Mutagene in a Human Hepatocellular Carcinoma." Molecular Biology & Medicine, vol. 7, no. 3, 1990, pp. 213-22.
Dejean A, de Thé H. Hepatitis B virus as an insertional mutagene in a human hepatocellular carcinoma. Mol Biol Med. 1990;7(3):213-22.
Dejean, A., & de Thé, H. (1990). Hepatitis B virus as an insertional mutagene in a human hepatocellular carcinoma. Molecular Biology & Medicine, 7(3), 213-22.
Dejean A, de Thé H. Hepatitis B Virus as an Insertional Mutagene in a Human Hepatocellular Carcinoma. Mol Biol Med. 1990;7(3):213-22. PubMed PMID: 2170809.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hepatitis B virus as an insertional mutagene in a human hepatocellular carcinoma. AU - Dejean,A, AU - de Thé,H, PY - 1990/6/1/pubmed PY - 1990/6/1/medline PY - 1990/6/1/entrez SP - 213 EP - 22 JF - Molecular biology & medicine JO - Mol Biol Med VL - 7 IS - 3 N2 - Chronic hepatitis B virus (HBV) infection is etiologically related to human hepatocellular carcinoma (HCC). Most HCCs contain integrated HBV DNA in the liver cellular DNA, suggesting that the integration may be involved in carcinogenesis. From a comparison of a single HBV integration site present in a hepatoma with the corresponding unoccupied site in the non-tumourous tissue of the same liver, we have shown that HBV DNA inserted in a putative cellular exon with striking similarity to the DNA-binding domain of the thyroid/steroid hormone receptors. The corresponding cDNA has been isolated (hap gene) and shown to encode the retinoic acid receptor. In the original patient, integration took place so that the first codons of the viral surface protein gene became fused in frame with most of the hap gene. Because retinoic acid is known to regulate the transcription of target genes crucial for cellular growth and differentiation, it is most probable that consequent to the HBV insertion, hap, usually transcribed at a very low level in normal hepatocytes, became inappropriately expressed as an altered chimaeric retinoic acid receptor, thus contributing to the cell transformation. These results strongly support the possibility that HBV may play a direct role in liver carcinogenesis by insertional mutagenesis. SN - 0735-1313 UR - https://www.unboundmedicine.com/medline/citation/2170809/Hepatitis_B_virus_as_an_insertional_mutagene_in_a_human_hepatocellular_carcinoma_ L2 - https://www.diseaseinfosearch.org/result/3332 DB - PRIME DP - Unbound Medicine ER -