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Generation and Molecular Characterization of Head and Neck Squamous Cell Lines of Fanconi Anemia Patients

Departments of ¹ Otolaryngology/Head-Neck Surgery, ² Pathology, and ³ Clinical Genetics and Human Genetics, Vrije University Medical Center, Amsterdam, The Netherlands; ⁴ Oregon Cancer Institute, Oregon Health and Science University, Portland, Oregon; ⁵ Department of Hematology and Institut Universitaire d'Hematologie, Hôpital Saint-Louis, Paris, France; and ⁶ Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Lund, Sweden

Requests for reprints: R.H. Brakenhoff, Department of Otolaryngology/Head-Neck Surgery, Vrije Universiteit Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. Phone 31-20-444-0953; Fax: 31-20-444-3688; E-mail: rh.brakenhoff{at}vumc.nl.

Patients with Fanconi anemia (FA) are prone to develop malignancies at an early age. Besides hematologic malignancies, squamous cell carcinomas in the anogenital region and head and neck are also frequently found in these patients. The aim of this study was to generate a panel of head and neck squamous cell carcinoma (HNSCC) cell lines and xenografts of FA HNSCC, and to characterize these cell lines in comparison with a panel of seven cell lines from patients with sporadic HNSCC. Analyses have been done on sensitivity to DNA cross-linking agents, loss of heterozygosity profile, TP53 mutations, TP53 polymorphisms and the presence of human papillomavirus. Four FA HNSCC cell lines were established. Sensitivity to DNA cross-linking agents (cisplatin) in the FA HNSCC cell lines was on average 10 times higher as compared with the sporadic HNSCC cell lines. Human papillomavirus was not detected in any of the FA or sporadic cell lines. No differences were found in loss of heterozygosity pattern, TP53 mutation frequency and TP53 polymorphism between FA and sporadic HNSCC cell lines. This is the first report on the generation of squamous cell lines of FA patients. The FA HNSCC cell lines we have generated may be utilized for future studies and might aid in the development of new preventive therapies for FA patients. The genetic characteristics of these cell lines suggest that FA HNSCC are not very different from sporadic HNSCC, except for the sensitivity to cisplatin which is consistent with the known cellular FA phenotype.

Key Words: Head and neck cancer • Fanconi anemia • Human papillomavirus • allelic loss • cell lines

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