Ser‐249<i>TP53</i> mutation in tumour and plasma DNA of hepatocellular carcinoma patients from a high incidence area in the Gambia, West Africa

Szymańska, Katarzyna; Lesi, Olufunmilayo; Kirk, Gregory D.; Sam, Omar; Tanière, Philippe; Scoazec, Jean‐Yves; Mendy, Maimuna; Friesen, Marlin D.; Whittle, Hilton; Montesano, Ruggero; Hainaut, Pierre

doi:10.1002/ijc.20103

Cited by 89 publications

(71 citation statements)

References 32 publications

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“…With the mechanistic understanding of the role of specific DNA-AFB1 adducts and the resulting formation of 249 ser mutations in hepatocytes (Smela et al, 2001), in conjunction with a significant majority of 249 ser TP53 mutations reported in the literature having been found in HCC (Hainaut and Hollstein, 2000), it is reasonable to deduce that the liver is the source of the 249 ser TP53 mutation that we detected. When we examined a limited number (17) of matched liver tumor/plasma pairs, we found concordance between tumor and plasma DNA findings in 88% (15) of cases (Szymanska et al, 2004). Similarly high concordance has been reported by Jackson et al (2001) among HCC cases from Qidong, China, a region with high HBV prevalence and AFB1 exposure.…”

Section: Discussionsupporting

confidence: 84%

“…In a preliminary study, we have shown that that 249 ser could be detected in plasma DNA from a proportion of HCC cases in The Gambia but not in HCC cases from Europe . We have also found that there was a concordance of 88% between the presence of 249 ser in the biopsy and in the plasma of the same HCC patient (Szymanska et al, 2004). In the present study, we have determined the presence of 249 ser in the plasma of over 600 subjects enrolled in a case-control study in The Gambia, to evaluate the individual and joint effects of plasma 249 ser and HBV markers on HCC development.…”

Section: Introductionmentioning

confidence: 78%

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249ser TP53 mutation in plasma DNA, hepatitis B viral infection, and risk of hepatocellular carcinoma

Lesi²,

et al. 2005

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Hepatocellular carcinoma (HCC) from regions with high dietary exposure to aflatoxins and endemic for hepatitis B virus (HBV) often contain a specific mutation at codon 249 in TP53 (249 ser ; AGG to AGT, Arg to Ser). This mutation is also detectable in circulating cell-free DNA from the plasma of HCC patients and healthy subjects in these regions. We have examined the joint effect of plasma 249 ser and HBV infection in a case-control study design involving 348 control, 98 cirrhotic, and 186 HCC participants from The Gambia, West Africa, an area of high HCC incidence. The 249 ser mutation was detected in 3.5% of controls, 15.3% of cirrhotics, and 39.8% of HCC cases (adjusted odds ratios (OR): 4.83, (95% confidence interval (CI): 1.71-13.7) for cirrhosis and 20.3 (8.19-50.0) for HCC). HBsAg positivity along with plasma 249 ser was observed in 45/183 (24.6%) HCC cases compared to only one (0.3%) control. Risk for HCC was associated with markers of HBV alone (OR: 10.0, 95% CI: 5.16-19.6), 249 ser alone (OR: 13.2, 95% CI: 4.99-35.0), and both markers present (OR: 399, 95% CI: 48.6-3270). These results suggest a multiplicative effect on HCC risk resulting from the mutational effect of aflatoxin on TP53, as monitored by detection of plasma 249 ser , with concomitant chronic infection with HBV.

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Section: Discussionsupporting

confidence: 84%

Section: Introductionmentioning

confidence: 78%

249ser TP53 mutation in plasma DNA, hepatitis B viral infection, and risk of hepatocellular carcinoma

Lesi²,

et al. 2005

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“…The size of the final PCR fragments were 237 bp (first PCR) and 177 bp (second PCR), respectively. TP53 mutation was analyzed by restriction fragment length polymorphism (RFLP) using a modified method described by Szymanska et al (2004 DOI:http://dx.doi.org/10.7314/APJCP.2013.14.6…”

Section: Detection Of R249s In Serummentioning

confidence: 99%

Hepatitis B Virus Genetic Variation and TP53 R249S Mutation in Patients with Hepatocellular Carcinoma in Thailand

Thongbai

Sa-nguanmoo²,

Kranokpiruk³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Chronic hepatitis B virus (HBV) infection and dietary exposure to aflatoxin B1 (AFB1) are major risk factors for hepatocellular carcinoma (HCC). The aim of this study was to evaluate the role of HBV genetic variation and the R249S mutation of the p53 gene, a marker of AFB1-induced HCC, in Thai patients chronically infected with HBV. Sixty-five patients with and 89 patients without HCC were included. Viral mutations and R249S mutation were characterized by direct sequencing and restriction fragment length polymorphism (RFLP) in serum samples, respectively. The prevalences of T1753C/A/G and A1762T/G1764A mutations in the basal core promotor (BCP) region were significantly higher in the HCC group compared to the non-HCC group. R249S mutation was detected in 6.2% and 3.4% of the HCC and non-HCC groups, respectively, which was not significantly different. By multiple logistic regression analysis, the presence of A1762T/G1764A mutations was independently associated with the risk of HCC in Thai patients.

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“…It occurs in more than 50% of patients with HCC from high incidence areas such as subSaharan Africa and East Asia (Hainaut and Hollstein 2000) and Ser-249 TP53 mutation, a missense mutation resulting in substitution of arginine with serine at codon 249, reflects high dietary exposure to aflatoxins (Hsu et al 1991). A few studies reported the feasibility of detection of Ser-249 mutation in cfDNA derived from plasma or serum of HCC patients (Szymańska et al 2004;Kirk et al 2005;Hosny et al 2008) highlighting the potential role of using circulating mutant DNA in diagnosis of HCC.…”

Section: Hepatocellular Carcinomamentioning

confidence: 99%

Current status and future potential of somatic mutation testing from circulating free DNA in patients with solid tumours

Aung

Board

Ellison

et al. 2010

HUGO J

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Genetic alterations can determine the natural history of cancer and its treatment response. With further advances in DNA sequencing technology, multiple novel genetic alterations will be discovered which could be exploited as prognostic, predictive and pharmacodynamic biomarkers in the development and use of cancer therapeutics. As such, the importance in clinical practice of efficient and robust somatic mutation testing in solid tumours cannot be overemphasized in the current era of personalized medicine. However, significant challenges remain regarding the testing of genetic biomarkers in clinical practice. Reliance on archived formalin fixed, paraffin embedded tumour, obtained from diagnostic biopsies, for testing somatic genetic alterations could restrict the scientific community in asking relevant questions about a patient's cancer biology. Problems inherent with using formalin fixed, archival tissue are well recognized and difficult to resolve. It could be argued that to achieve rapid and efficient incorporation of genetic biomarkers into clinical practice, somatic mutation testing in cancer patients should be simpler, less invasive using a readily available clinical sample, whilst maintaining robustness and reproducibility. In this regard, use of circulating free DNA (cfDNA) from plasma or serum as an alternative and/or additional source of DNA to test cancer specific genetic alterations is an attractive proposition. In light of encouraging results from recent studies, this mini review will discuss the current role and future potential of somatic mutation testing from circulating or cell free DNA derived from the blood of patients with solid tumours.

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Ser‐249TP53 mutation in tumour and plasma DNA of hepatocellular carcinoma patients from a high incidence area in the Gambia, West Africa

Cited by 89 publications

References 32 publications

249ser TP53 mutation in plasma DNA, hepatitis B viral infection, and risk of hepatocellular carcinoma

249ser TP53 mutation in plasma DNA, hepatitis B viral infection, and risk of hepatocellular carcinoma

Hepatitis B Virus Genetic Variation and TP53 R249S Mutation in Patients with Hepatocellular Carcinoma in Thailand

Current status and future potential of somatic mutation testing from circulating free DNA in patients with solid tumours

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