Journal of the National Cancer Institute Advance Access published online on November 11, 2008
JNCI Journal of the National Cancer Institute, doi:10.1093/jnci/djn366
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© The Author 2008. Published by Oxford University Press.
Clinical and Molecular Characteristics of Squamous Cell Carcinomas From Fanconi Anemia Patients
Affiliations of authors: Department of Otolaryngology/Head and Neck Surgery, Section Tumor Biology (HJTvZ, TW, CRL, RHB), Department of Pathology (PJFS, EB), Department of Clinical Genetics (HJ), VU University Medical Center, Amsterdam, the Netherlands; Department of Hematology, Saint Louis Hospital, Paris, France (EG, J. Soulier); Department of Genetics and Microbiology, Autonomous University of Barcelona and Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, Bellaterra, Spain (J. Surralles, MC); Department of Pathology, University Medical Center, Groningen, the Netherlands (JEvdW); Department of Otorhinolaryngology/Head-Neck Surgery, University Hospital, Lund, Sweden (JW); Department of Otolaryngology/Head-Neck Surgery, Johns Hopkins Medical Institute, Baltimore, MD (JC); Children’s Clinic, Heinrich-Heine University, Düsseldorf, Germany (EV); Fanconi-Anämie Hilfe e.V., Unna-Siddinghausen, Germany (RD); Department of Pediatrics, Charité-CVK, University of Medicine, Berlin, Germany (WE)
Correspondence to: Ruud H. Brakenhoff, PhD, Department of Otolaryngology/Head-Neck Surgery, Section Tumor Biology, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, the Netherlands (e-mail: rh.brakenhoff{at}vumc.nl).
Fanconi anemia is a recessively inherited disease that is characterized by congenital abnormalities, bone marrow failure, and a predisposition to develop cancer, particularly squamous cell carcinomas (SCCs) in the head and neck and anogenital regions. Previous studies of Fanconi anemia SCCs, mainly from US patients, revealed the presence of high-risk human papillomavirus (HPV) DNA in 21 (84%) of 25 tumors analyzed. We examined a panel of 21 SCCs mainly from European Fanconi anemia patients (n = 19 FA patients; 16 head and neck squamous cell carcinomas [HNSCCs], 2 esophageal SCCs, and 3 anogenital SCCs) for their clinical and molecular characteristics, including patterns of allelic loss, TP53 mutations, and the presence of HPV DNA by GP5+/6+ polymerase chain reaction. HPV DNA was detected in only two (10%) of 21 tumors (both anogenital SCCs) but in none of the 16 HNSCCs. Of the 18 tumors analyzed, 10 contained a TP53 mutation. The patterns of allelic loss were comparable to those generally found in sporadic SCCs. Our data show that HPV does not play a major role in squamous cell carcinogenesis in this cohort of Fanconi anemia patients and that the Fanconi anemia SCCs are genetically similar to sporadic SCCs despite having a different etiology.
| CONTEXT AND CAVEATS Prior knowledge Fanconi anemia is a rare recessively inherited disease that is characterized by congenital abnormalities, bone marrow failure, and a predisposition to develop cancer, particularly squamous cell carcinomas (SCCs) in the head and neck (HNSCCs) and anogenital regions. In previous studies of mostly US Fanconi anemia patients, high-risk human papillomavirus (HPV) DNA was detected in the majority of the SCCs analyzed. Study design An examination of the clinical and molecular characteristics of 21 SCCs (16 HNSCCs, 2 esophageal SCCs, and 3 anogenital SCCs) from 19 mostly European Fanconi anemia patients, including the presence of HPV DNA, allelic loss patterns, and TP53 mutations. Contribution HPV DNA was detected in only two of 21 tumors (both anogenital SCCs) but in none of the 16 HNSCCs. Ten of 18 SCCs analyzed contained a TP53 mutation. The patterns of allelic loss for the Fanconi anemia SCCs were similar to those found in sporadic SCCs, despite the differing etiologies of these tumors. Implications The role of HPV infection in squamous cell carcinogenesis may differ among cohorts of Fanconi anemia patients. Limitations The number of tumor samples analyzed was small. From the Editors
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Manuscript received April 8, 2008; revised August 26, 2008; accepted September 12, 2008.
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