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.
authors: Laboratory of Epithelial Cancer Biology, Division of Head and Neck Surgery, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors: David I
authors: DI
authors: Kutler
authors: Volkert B
authors: VB
authors: Wreesmann
authors: Andy
authors: A
authors: Goberdhan
authors: Leah
authors: L
authors: Ben-Porat
authors: Jaya
authors: J
authors: Satagopan
authors: Ivan
authors: I
authors: Ngai
authors: Andrew G
authors: AG
authors: Huvos
authors: Philip
authors: P
authors: Giampietro
authors: Orna
authors: O
authors: Levran
authors: Kanan
authors: K
authors: Pujara
authors: Rafaella
authors: R
authors: Diotti
authors: Diane
authors: D
authors: Carlson
authors: Laryssa A
authors: LA
authors: Huryn
authors: Arleen D
authors: AD
authors: Auerbach
authors: Bhuvanesh
authors: B
authors: Singh
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000821:virology*; D004279:DNA, Viral / Q000302:isolation & purification*; D005199:Fanconi Anemia / Q000150:complications*; D005838:Genotype; D006801:Humans; D027383:Papillomaviridae / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D004279:DNA, Viral; D016159:Tumor Suppressor Protein p53