Tags

Type your tag names separated by a space and hit enter

P53 tumor suppressor gene mutations in hepatocellular carcinoma patients in India.
Cancer. 2000 Apr 01; 88(7):1565-73.C

Abstract

BACKGROUND

Specific mutations of the p53 tumor suppressor gene in hepatocellular carcinoma (HCC) have been reported from several parts of the world, but to the authors' knowledge to date the status of this gene has not been studied in HCC patients in India, where HCC is one of the major cancers and the frequency of chronic hepatitis B virus (HBV) as well as hepatitis C virus (HCV) infection and exposure to dietary aflatoxin B(1) is very high. The most frequent mutation of the p53 gene in HCC is an AGG(Arg) to AGT(Ser) missense mutation at codon 249 of exon 7.

METHODS

Liver biopsy specimens from 21 HCC patients and 10 healthy controls were obtained through surgery or by needle biopsy technique. Phenol-chloroform-extracted DNA specimens were employed for the detection of HBV infection and p53 gene mutations. Nucleotide mutations of exons 4-9 of the p53 gene were analyzed by polymerase chain reaction (PCR), single strand confirmation polymorphism, and direct sequencing. Third-generation sandwich enzyme-linked immunosorbent assay (ELISA) was used for the serologic detection of HBV and HCV infection.

RESULTS

Analysis of exons 4-9 of the p53 gene revealed only 3 mutations (3 of 21 specimens, 14.28%; 95% confidence interval, -0.7-29.3), 2 mutations at codon 249 showing G-->T transversions, and 1 mutation (4.7%) at codon 250 with a C-->T transition. The base substitutions at the third base of codon 249 resulted in a missense mutation leading to a change in amino acid from arginine to serine whereas at codon 250 it caused a change from proline to serine. Dot blot hybridization and PCR for HBV DNA from HCCs revealed 58.8% (10 of 17 specimens) and 90. 47% (19 of 21 specimens), positivity, respectively. ELISA for hepatitis B virus surface antigen in serum showed a positivity of 71. 42% (15 of 21 specimens), but there was only 40% positivity (8 of 20 specimens) for hepatitis B virus envelope antigen whereas 6 of 17 patients (35.29%) showed the presence of antibodies against hepatitis B virus envelope protein. No patient was found to be positive for the HCV antibody.

CONCLUSIONS

The very low frequency of p53 mutations and the extremely high frequency of HBV infection (> 90%) in HCC indicate that the mutations in the p53 gene frequently found in HCC reported from different endemic areas of the world may not play a direct role in the development of HCC in India. HBV infection and, possibly, exposure to the dietary aflatoxin B(1) appear to play major roles in the molecular pathogenesis of HCC in India.

Authors+Show Affiliations

Division of Molecular Oncology, Institute of Cytology and Preventive Oncology, Maulana Azad Medical College Campus, Bahadur Shah Zafar Marg, New Delhi, India.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

10738214

Citation

Katiyar, S, et al. "P53 Tumor Suppressor Gene Mutations in Hepatocellular Carcinoma Patients in India." Cancer, vol. 88, no. 7, 2000, pp. 1565-73.
Katiyar S, Dash BC, Thakur V, et al. P53 tumor suppressor gene mutations in hepatocellular carcinoma patients in India. Cancer. 2000;88(7):1565-73.
Katiyar, S., Dash, B. C., Thakur, V., Guptan, R. C., Sarin, S. K., & Das, B. C. (2000). P53 tumor suppressor gene mutations in hepatocellular carcinoma patients in India. Cancer, 88(7), 1565-73.
Katiyar S, et al. P53 Tumor Suppressor Gene Mutations in Hepatocellular Carcinoma Patients in India. Cancer. 2000 Apr 1;88(7):1565-73. PubMed PMID: 10738214.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - P53 tumor suppressor gene mutations in hepatocellular carcinoma patients in India. AU - Katiyar,S, AU - Dash,B C, AU - Thakur,V, AU - Guptan,R C, AU - Sarin,S K, AU - Das,B C, PY - 2000/3/30/pubmed PY - 2000/4/29/medline PY - 2000/3/30/entrez SP - 1565 EP - 73 JF - Cancer JO - Cancer VL - 88 IS - 7 N2 - BACKGROUND: Specific mutations of the p53 tumor suppressor gene in hepatocellular carcinoma (HCC) have been reported from several parts of the world, but to the authors' knowledge to date the status of this gene has not been studied in HCC patients in India, where HCC is one of the major cancers and the frequency of chronic hepatitis B virus (HBV) as well as hepatitis C virus (HCV) infection and exposure to dietary aflatoxin B(1) is very high. The most frequent mutation of the p53 gene in HCC is an AGG(Arg) to AGT(Ser) missense mutation at codon 249 of exon 7. METHODS: Liver biopsy specimens from 21 HCC patients and 10 healthy controls were obtained through surgery or by needle biopsy technique. Phenol-chloroform-extracted DNA specimens were employed for the detection of HBV infection and p53 gene mutations. Nucleotide mutations of exons 4-9 of the p53 gene were analyzed by polymerase chain reaction (PCR), single strand confirmation polymorphism, and direct sequencing. Third-generation sandwich enzyme-linked immunosorbent assay (ELISA) was used for the serologic detection of HBV and HCV infection. RESULTS: Analysis of exons 4-9 of the p53 gene revealed only 3 mutations (3 of 21 specimens, 14.28%; 95% confidence interval, -0.7-29.3), 2 mutations at codon 249 showing G-->T transversions, and 1 mutation (4.7%) at codon 250 with a C-->T transition. The base substitutions at the third base of codon 249 resulted in a missense mutation leading to a change in amino acid from arginine to serine whereas at codon 250 it caused a change from proline to serine. Dot blot hybridization and PCR for HBV DNA from HCCs revealed 58.8% (10 of 17 specimens) and 90. 47% (19 of 21 specimens), positivity, respectively. ELISA for hepatitis B virus surface antigen in serum showed a positivity of 71. 42% (15 of 21 specimens), but there was only 40% positivity (8 of 20 specimens) for hepatitis B virus envelope antigen whereas 6 of 17 patients (35.29%) showed the presence of antibodies against hepatitis B virus envelope protein. No patient was found to be positive for the HCV antibody. CONCLUSIONS: The very low frequency of p53 mutations and the extremely high frequency of HBV infection (> 90%) in HCC indicate that the mutations in the p53 gene frequently found in HCC reported from different endemic areas of the world may not play a direct role in the development of HCC in India. HBV infection and, possibly, exposure to the dietary aflatoxin B(1) appear to play major roles in the molecular pathogenesis of HCC in India. SN - 0008-543X UR - https://www.unboundmedicine.com/medline/citation/10738214/P53_tumor_suppressor_gene_mutations_in_hepatocellular_carcinoma_patients_in_India_ L2 - https://medlineplus.gov/livercancer.html DB - PRIME DP - Unbound Medicine ER -