BACKGROUND: Much of our understanding of human cancer has come from studies of the hereditary cancer predisposition syndromes. Fanconi anemia (FA) is an autosomal recessive disorder characterized by cellular hypersensitivity to DNA cross-linking agents (mitomycin, cisplatin), progressive bone marrow failure, and cancer predisposition. Accumulating evidence suggests that patients with FA are predisposed to development of squamous cell carcinomas, particularly those involving the upper aerodigestive tract. extrapolation of this link to cancers in the general population may be of clinical interest. The purpose of this study was to determine whether dysregulation of FA genes occurs in sporadic head and neck squamous cell carcinoma (HNSCC). MAIN OUTCOME MEASURES: We used the immunoblot-based FANCD2 monoubiquitination assay to assess for aberrations in the FA pathway in 13 sporadic HNSCC cell lines. Using quantitative real-time PCR, we assessed the expression of the FA genes FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCJ, FANCL and FANCM in 13 HNSCC cell lines and 49 samples of oral tongue cancer. RESULTS: Defective FANCD2 monoubiquitination was identified in 2 cell lines. Compared to normal human keratinocytes, downregulation of FA genes was observed in 5 cell lines. Downregulation of FA genes was also seen in 50% of tongue carcinoma samples compared to matched normal oral mucosa. Analysis of clinicopathological data demonstrated that downregulation of the FA pathway was associated with a young age and aggressive clinical phenotype. CONCLUSION: Our data suggest that the FA pathway is dysregulated in HNSCC from patients without FA. The implications of this association merit further study.

[Proc Amer Assoc Cancer Res, Volume 47, 2006]