Quantitative analysis of plasma TP53 249Ser-mutated DNA by electrospray ionization mass spectrometry

Matilde E. Lleonart, Gregory D Kirk, Stephanie Villar, Olufunmilayo A. Lesi, Abhijit Dasgupta, James J. Goedert, Maimuna Mendy, Monica C. Hollstein, Ruggero Montesano, John Davis Groopman, Pierre Hainaut, Marlin D. Friesen

Research output: Contribution to journalArticle

Abstract

A mutation in codon 249 of the TP53 gene (219Ser), related to aflatoxin B1 exposure, has previously been associated with hepatocellular carcinoma risk. Using a novel internal standard plasmid, plasma concentrations of 249Ser-mutated DNA were quantified by electrospray ionization mass spectrometry in 89 hepatocellular carcinoma cases, 42 cirrhotic patients, and 131 nonliver diseased control subjects, all from highly aflatoxin-exposed regions of The Gambia. The hepatocellular carcinoma cases had higher median plasma concentrations of 249Ser (2,800 copies/mL; interquartile range: 500-11,000) compared with either cirrhotic (500 copies/mL; interquartile range: 500-2,600) or control subjects (500 copies/mL; interquartile range: 500-2,000; P <0.05). About half (52%) of the hepatocellular carcinoma cases had >2,500 copies of 249Ser/mL plasma, corresponding to the prevalence of this mutation in liver tumors in The Gambia. In comparison, only 15% of control group and 26% of cirrhotic participants exceeded this level (P <0.05). Further subset analysis revealed a statistically significant, quantitative relation between diagnosis of hepatocellular carcinoma and levels of 249Ser detected at 2,501 to 10,000 copies/mL plasma (odds ratio, 3.8; 95% confidence interval, 1.3-10.9) and at > 10,000 copies/mL plasma (odds ratio, 62; 95% confidence interval, 4.7-820) when compared with control subjects and after adjusting for age, gender, recruitment site, hepatitis B and C serologic status, and total DNA concentration. Levels of > 10,000 copies of 249Ser/mL plasma were also significantly associated with the diagnosis of hepatocellular carcinoma (odds ratio, 15; 95% confidence interval, 1.6-140) when compared with cirrhotic patients. Potential applications for the quantification of 249Ser DNA in plasma include estimation of long-term, cumulative aflatoxin exposure and selection of appropriate high-risk individuals for targeted intervention.

Original languageEnglish (US)
Pages (from-to)2956-2962
Number of pages7
JournalCancer Epidemiology Biomarkers and Prevention
Volume14
Issue number12
DOIs
StatePublished - Dec 2005

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Electrospray Ionization Mass Spectrometry
Hepatocellular Carcinoma
DNA
Gambia
Aflatoxins
Odds Ratio
Confidence Intervals
Mutation
Aflatoxin B1
p53 Genes
Hepatitis C
Hepatitis B
Codon
Plasmids
Control Groups
Liver
Neoplasms

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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Quantitative analysis of plasma TP53 249Ser-mutated DNA by electrospray ionization mass spectrometry. / Lleonart, Matilde E.; Kirk, Gregory D; Villar, Stephanie; Lesi, Olufunmilayo A.; Dasgupta, Abhijit; Goedert, James J.; Mendy, Maimuna; Hollstein, Monica C.; Montesano, Ruggero; Groopman, John Davis; Hainaut, Pierre; Friesen, Marlin D.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 14, No. 12, 12.2005, p. 2956-2962.

Research output: Contribution to journalArticle

Lleonart, ME, Kirk, GD, Villar, S, Lesi, OA, Dasgupta, A, Goedert, JJ, Mendy, M, Hollstein, MC, Montesano, R, Groopman, JD, Hainaut, P & Friesen, MD 2005, 'Quantitative analysis of plasma TP53 249Ser-mutated DNA by electrospray ionization mass spectrometry', Cancer Epidemiology Biomarkers and Prevention, vol. 14, no. 12, pp. 2956-2962. https://doi.org/10.1158/1055-9965.EPI-05-0612
Lleonart, Matilde E. ; Kirk, Gregory D ; Villar, Stephanie ; Lesi, Olufunmilayo A. ; Dasgupta, Abhijit ; Goedert, James J. ; Mendy, Maimuna ; Hollstein, Monica C. ; Montesano, Ruggero ; Groopman, John Davis ; Hainaut, Pierre ; Friesen, Marlin D. / Quantitative analysis of plasma TP53 249Ser-mutated DNA by electrospray ionization mass spectrometry. In: Cancer Epidemiology Biomarkers and Prevention. 2005 ; Vol. 14, No. 12. pp. 2956-2962.
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abstract = "A mutation in codon 249 of the TP53 gene (219Ser), related to aflatoxin B1 exposure, has previously been associated with hepatocellular carcinoma risk. Using a novel internal standard plasmid, plasma concentrations of 249Ser-mutated DNA were quantified by electrospray ionization mass spectrometry in 89 hepatocellular carcinoma cases, 42 cirrhotic patients, and 131 nonliver diseased control subjects, all from highly aflatoxin-exposed regions of The Gambia. The hepatocellular carcinoma cases had higher median plasma concentrations of 249Ser (2,800 copies/mL; interquartile range: 500-11,000) compared with either cirrhotic (500 copies/mL; interquartile range: 500-2,600) or control subjects (500 copies/mL; interquartile range: 500-2,000; P <0.05). About half (52{\%}) of the hepatocellular carcinoma cases had >2,500 copies of 249Ser/mL plasma, corresponding to the prevalence of this mutation in liver tumors in The Gambia. In comparison, only 15{\%} of control group and 26{\%} of cirrhotic participants exceeded this level (P <0.05). Further subset analysis revealed a statistically significant, quantitative relation between diagnosis of hepatocellular carcinoma and levels of 249Ser detected at 2,501 to 10,000 copies/mL plasma (odds ratio, 3.8; 95{\%} confidence interval, 1.3-10.9) and at > 10,000 copies/mL plasma (odds ratio, 62; 95{\%} confidence interval, 4.7-820) when compared with control subjects and after adjusting for age, gender, recruitment site, hepatitis B and C serologic status, and total DNA concentration. Levels of > 10,000 copies of 249Ser/mL plasma were also significantly associated with the diagnosis of hepatocellular carcinoma (odds ratio, 15; 95{\%} confidence interval, 1.6-140) when compared with cirrhotic patients. Potential applications for the quantification of 249Ser DNA in plasma include estimation of long-term, cumulative aflatoxin exposure and selection of appropriate high-risk individuals for targeted intervention.",
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