Tags

Type your tag names separated by a space and hit enter

p53 gene mutation and integrated hepatitis B viral DNA sequences in human liver cancer cell lines.
Carcinogenesis. 1993 May; 14(5):987-92.C

Abstract

A G:C-->T:A mutational hotspot at codon 249 of the p53 tumor suppressor gene has previously been identified in hepatocellular carcinoma (HCC) of patients from Qidong, China and southern Africa in which aflatoxin B1 (AFB1) and hepatitis B virus (HBV) are known synergistic risk factors. We have examined p53 mutation patterns of HCC from geographic areas in which the risk factors vary. Nine HCC lines and four hepatoblastoma lines (HB) were examined for p53 gene mutations and the relationship with HBV infection. Five of the nine HCC lines had homozygous mutation or deletion randomly distributed in exons 6-8, whereas none of the four HB cell lines had p53 mutations. One of the four HB lines (HepG2) had an N-ras mutation at codon 61 position 2. The p53 point mutations in the three HCC cell lines from Japan resulted in the amino acid changes of cysteine for tyrosine in cell line HuH 7 at codon 220 (A:T-->G:C), alanine for glycine in cell line HLF at codon 244 (G:C-->C:G), and serine for arginine in cell line HLE at codon 249 (G:C-->C:G). In addition, the deletion of 18 base pairs from codon 264 position 3 to codon 270 position 1 has resulted in the deletion of Leu-Gly-Arg-Asn-Ser-Phe from the amino acids sequences 256-270 in the Japanese cell line HuH 4. The cell line PLC/PRF/5 that showed p53 mutation at codon 249 (G:C-->T:A) with substitution of serine for arginine was derived from a South African patient. Our results indicate that whereas the p53 gene is not mutated in the HB cell lines, the HCC cell lines frequently contain an abnormal p53 gene. In addition, p53 point mutations were not detected in the four Japanese HCC cell lines that were positive for genomic integration of HBV X-gene and surface antigen gene. The three Japanese HCC cell lines with p53 mutations did not contain HBV sequences, indicating that hepatocarcinogenesis associated with p53 mutation does not require the genomic integration of HBV sequences.

Authors+Show Affiliations

Department of Pathology, University of Maryland School of Medicine, Baltimore 21201.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

8389256

Citation

Hsu, I C., et al. "P53 Gene Mutation and Integrated Hepatitis B Viral DNA Sequences in Human Liver Cancer Cell Lines." Carcinogenesis, vol. 14, no. 5, 1993, pp. 987-92.
Hsu IC, Tokiwa T, Bennett W, et al. P53 gene mutation and integrated hepatitis B viral DNA sequences in human liver cancer cell lines. Carcinogenesis. 1993;14(5):987-92.
Hsu, I. C., Tokiwa, T., Bennett, W., Metcalf, R. A., Welsh, J. A., Sun, T., & Harris, C. C. (1993). P53 gene mutation and integrated hepatitis B viral DNA sequences in human liver cancer cell lines. Carcinogenesis, 14(5), 987-92.
Hsu IC, et al. P53 Gene Mutation and Integrated Hepatitis B Viral DNA Sequences in Human Liver Cancer Cell Lines. Carcinogenesis. 1993;14(5):987-92. PubMed PMID: 8389256.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - p53 gene mutation and integrated hepatitis B viral DNA sequences in human liver cancer cell lines. AU - Hsu,I C, AU - Tokiwa,T, AU - Bennett,W, AU - Metcalf,R A, AU - Welsh,J A, AU - Sun,T, AU - Harris,C C, PY - 1993/5/1/pubmed PY - 1993/5/1/medline PY - 1993/5/1/entrez SP - 987 EP - 92 JF - Carcinogenesis JO - Carcinogenesis VL - 14 IS - 5 N2 - A G:C-->T:A mutational hotspot at codon 249 of the p53 tumor suppressor gene has previously been identified in hepatocellular carcinoma (HCC) of patients from Qidong, China and southern Africa in which aflatoxin B1 (AFB1) and hepatitis B virus (HBV) are known synergistic risk factors. We have examined p53 mutation patterns of HCC from geographic areas in which the risk factors vary. Nine HCC lines and four hepatoblastoma lines (HB) were examined for p53 gene mutations and the relationship with HBV infection. Five of the nine HCC lines had homozygous mutation or deletion randomly distributed in exons 6-8, whereas none of the four HB cell lines had p53 mutations. One of the four HB lines (HepG2) had an N-ras mutation at codon 61 position 2. The p53 point mutations in the three HCC cell lines from Japan resulted in the amino acid changes of cysteine for tyrosine in cell line HuH 7 at codon 220 (A:T-->G:C), alanine for glycine in cell line HLF at codon 244 (G:C-->C:G), and serine for arginine in cell line HLE at codon 249 (G:C-->C:G). In addition, the deletion of 18 base pairs from codon 264 position 3 to codon 270 position 1 has resulted in the deletion of Leu-Gly-Arg-Asn-Ser-Phe from the amino acids sequences 256-270 in the Japanese cell line HuH 4. The cell line PLC/PRF/5 that showed p53 mutation at codon 249 (G:C-->T:A) with substitution of serine for arginine was derived from a South African patient. Our results indicate that whereas the p53 gene is not mutated in the HB cell lines, the HCC cell lines frequently contain an abnormal p53 gene. In addition, p53 point mutations were not detected in the four Japanese HCC cell lines that were positive for genomic integration of HBV X-gene and surface antigen gene. The three Japanese HCC cell lines with p53 mutations did not contain HBV sequences, indicating that hepatocarcinogenesis associated with p53 mutation does not require the genomic integration of HBV sequences. SN - 0143-3334 UR - https://www.unboundmedicine.com/medline/citation/8389256/p53_gene_mutation_and_integrated_hepatitis_B_viral_DNA_sequences_in_human_liver_cancer_cell_lines_ L2 - https://academic.oup.com/carcin/article-lookup/doi/10.1093/carcin/14.5.987 DB - PRIME DP - Unbound Medicine ER -