Human papillomavirus DNA and p53 polymorphisms in squamous cell carcinomas from Fanconi anemia patients Journal Article


Authors: Kutler, D. I.; Wreesmann, V. B.; Goberdhan, A.; Ben-Porat, L.; Satagopan, J.; Ngai, I.; Huvos, A. G.; Giampietro, P.; Levran, O.; Pujara, K.; Diotti, R.; Carlson, D.; Huryn, L. A.; Auerbach, A. D.; Singh, B.
Article Title: Human papillomavirus DNA and p53 polymorphisms in squamous cell carcinomas from Fanconi anemia patients
Abstract: Fanconi anemia is an autosomal recessive disorder characterized by congenital malformations, bone marrow failure, and the development of squamous cell carcinomas (SCCs) and other cancers. Recent clinicopathologic evidence has raised the possibility that an environmental factor such as human papillomavirus (HPV) may be involved in the pathogenesis of SCCs in Fanconi anemia patients. Given the high prevalence of p53 mutations in SCCs among the general population and the lack of p53 mutations in HPV-related carcinogenesis, we evaluated the role of HPV and p53 mutations and polymorphisms in SCC from Fanconi anemia patients. We used polymerase chain reaction (PCR) screening and real-time PCR to detect and quantify HPV DNA in DNA extracted from microdissected SCCs obtained from 24 Fanconi anemia patients (n = 25 SCCs; case subjects) and 50 age-, sex-, and tumor site-matched SCC patients without Fanconi anemia (n = 50 SCCs; control subjects). We PCR-amplified and sequenced exons 4-9 of the p53 gene from SCC DNA. We detected HPV DNA in 84% of the SCC specimens from the case subjects and in 36% of the SCC specimens from the control subjects (P<.001). The prevalence of p53 mutations in SCCs from the case subjects (0%, 0/25) was statistically significantly lower than that of SCCs from the control subjects (36%, 12/33; P<.001). A greater proportion of patients with Fanconi anemia and SCC were homozygous for Arg72, a p53 polymorphism that may be associated with increased risk for HPV-associated human malignancies, than an ethnically-matched cohort of Fanconi anemia patients without SCC (75% versus 51%; P = .05). These data suggest that Fanconi anemia is associated with increased susceptibility to HPV-induced carcinogenesis.
Keywords: adolescent; adult; clinical article; controlled study; gene mutation; gene sequence; clinical feature; squamous cell carcinoma; carcinoma, squamous cell; cancer risk; polymerase chain reaction; cancer susceptibility; gene amplification; prevalence; cohort analysis; genotype; protein p53; carcinogenesis; homozygosity; statistical analysis; quantitative analysis; tumor suppressor protein p53; dna, viral; ethnic difference; genetic screening; dna extraction; polymorphism, genetic; genetic polymorphism; wart virus; fanconi anemia; autosomal recessive disorder; virus dna; bone marrow depression; congenital malformation; papillomaviridae; cancer; humans; human; male; female; priority journal; article
Journal Title: JNCI: Journal of the National Cancer Institute
Volume: 95
Issue: 22
ISSN: 0027-8874
Publisher: Oxford University Press  
Date Published: 2003-11-19
Start Page: 1718
End Page: 1721
Language: English
PUBMED: 14625263
PROVIDER: scopus
DOI: 10.1093/jnci/djg091
DOI/URL:
Notes: Export Date: 12 September 2014 -- Source: Scopus
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MSK Authors
  1. David Kutler
    13 Kutler
  2. Jaya M Satagopan
    141 Satagopan
  3. Bhuvanesh Singh
    242 Singh
  4. Diane Carlson
    52 Carlson
  5. Laryssa A Huryn
    3 Huryn
  6. Andrew G Huvos
    289 Huvos
  7. Ivan Ngai
    17 Ngai