Carcinogenesis Advance Access published online on July 17, 2003
Carcinogenesis, doi:10.1093/carcin/bgg101
© 2003 by Oxford University Press
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MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
1 Johns Hopkins University, Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA
* Corresponding author. E-mail: jgroopma{at}jhsph.edu.
Received 11 February 2003
; revised 29 April 2003
; accepted 7 June 2003
A specific missense mutation in the p53 tumor suppressor gene at codon 249 has been reported in over 50% of hepatocellular carcinoma (HCC) tumors and in paired blood samples from areas of high dietary exposure to aflatoxin B1, including Qidong, P.R.C. Using a combination of pre-digestion with HaeIII, PCR and mass spectrometry, the temporality of this mutation in plasma before and after the clinical diagnosis of HCC was examined. Sixteen liver cancer cases, diagnosed between 1997 and 2001, were selected from a prospective cohort of 1638 high-risk individuals in Qidong on the basis of available annual plasma samples spanning the years before and after diagnosis. The codon 249 mutation was detected in plasma samples obtained after diagnosis in 7 of the 15 cases (46.7%) with PCR amplifiable DNA, which is in accord with the reported prevalence of this mutation in HCC. The persistent detection of this mutation in plasma collected annually following diagnosis was statistically significant (p=0.024, two-tailed) in repetitive samples following diagnosis. Moreover, the mutation was detected in plasma of 4 of 8 cases positive at time of diagnosis at least one year and in one case five years prior to diagnosis. Tracking of the marker in pre-diagnostic samples was borderline statistically significant (p=0.066). None of the eighteen healthy US control plasma samples had any detectable mutations. We have therefore found that pre-diagnosis biomarkers of specific p53 mutations can be measured in plasma and this suggests a paradigm for developing these markers for use in prevention and intervention trials.
short oligonucleotide mass analysis, mutation detection, p53 mutations, hepatocellular carcinoma, electrospray ionization mass spectrometry
Prospective detection of codon 249 mutations in p53 in plasma of hepatocellular carcinoma patients
2 Qidong Liver Cancer Institute, Qidong, 226200, Jiangsu Province, People's Republic of China
3 Shanghai Cancer Institute, Shanghai, 200032, People's Republic of China
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