Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2009 Jun 26:9:204.
doi: 10.1186/1471-2407-9-204.

249 TP53 mutation has high prevalence and is correlated with larger and poorly differentiated HCC in Brazilian patients

Jeronimo A Nogueira  1 , Suzane K Ono-Nita, Marcelo E Nita, Marcelo M T de Souza, Eliane P do Carmo, Evandro S Mello, Cristovan Scapulatempo, Denise C Paranaguá-Vezozzo, Flair J Carrilho, Venancio A F Alves
Affiliations

249 TP53 mutation has high prevalence and is correlated with larger and poorly differentiated HCC in Brazilian patients

Jeronimo A Nogueira et al. BMC Cancer. .

Abstract

Background: Ser-249 TP53 mutation (249(Ser)) is a molecular evidence for aflatoxin-related carcinogenesis in Hepatocellular Carcinoma (HCC) and it is frequent in some African and Asian regions, but it is unusual in Western countries. HBV has been claimed to add a synergic effect on genesis of this particular mutation with aflatoxin. The aim of this study was to investigate the frequency of 249(Ser) mutation in HCC from patients in Brazil.

Methods: We studied 74 HCC formalin fixed paraffin blocks samples of patients whom underwent surgical resection in Brazil. 249(Ser) mutation was analyzed by RFLP and DNA sequencing. HBV DNA presence was determined by Real-Time PCR.

Results: 249(Ser) mutation was found in 21/74 (28%) samples while HBV DNA was detected in 13/74 (16%). 249Ser mutation was detected in 21/74 samples by RFLP assay, of which 14 were confirmed by 249(Ser) mutant-specific PCR, and 12 by nucleic acid sequencing. All HCC cases with p53-249ser mutation displayed also wild-type p53 sequences. Poorly differentiated HCC was more likely to have 249(Ser) mutation (OR = 2.415, 95% CI = 1.001 - 5.824, p = 0.05). The mean size of 249(Ser) HCC tumor was 9.4 cm versus 5.5 cm on wild type HCC (p = 0.012). HBV DNA detection was not related to 249(Ser) mutation.

Conclusion: Our results indicate that 249(Ser) mutation is a HCC important factor of carcinogenesis in Brazil and it is associated to large and poorly differentiated tumors.

PubMed Disclaimer

Figures

Figure 1
Figure 1
A. RFLPs of PCR-amplified fragments obtained with HaeIII. There are 2 genotypes represented by the gel picture, wild type (a, c and d) where a 158 bp band is absent and 249Ser (b, e and f) where the 158 pb fragment can be observed. 1B. Representative eletropherograms of TP53 sequence. Nucleotide sequence of a mutated sample on top, showing the G → T transversion (AGT) when compared with a wild type exon 7 below (AGG).
Figure 2
Figure 2
PCR-amplified products with mutant-specific primer for identification of mutant TP-53 allele (lower 155 bp band). Lane 15 is a wild type control.
See this image and copyright information in PMC

References

    1. Strosnider H, Azziz-Baumgartner E, Banziger M, Bhat RV, Breiman R, Brune MN, DeCock K, Dilley A, Groopman J, Hell K. Workgroup report: public health strategies for reducing aflatoxin exposure in developing countries. Environmental health perspectives. 2006;114(12):1898–1903. - PMC - PubMed
    1. Thorgeirsson SS, Grisham JW. Molecular pathogenesis of human hepatocellular carcinoma. Nature genetics. 2002;31(4):339–346. doi: 10.1038/ng0802-339. - DOI - PubMed
    1. Nita ME, Alves VA, Carrilho FJ, Ono-Nita SK, Mello ES, Gama-Rodrigues JJ. Molecular aspects of hepatic carcinogenesis. Revista do Instituto de Medicina Tropical de Sao Paulo. 2002;44(1):39–48. - PubMed
    1. Rocken C, Carl-McGrath S. Pathology and pathogenesis of hepatocellular carcinoma. Digestive diseases (Basel, Switzerland) 2001;19(4):269–278. - PubMed
    1. El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132(7):2557–2576. doi: 10.1053/j.gastro.2007.04.061. - DOI - PubMed

Publication types

MeSH terms