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Higher Frequency of Alterations in the p16/CDKN2 Gene in Squamous Cell Carcinoma Cell Lines Than in Primary Tumors of the Head and Neck¹

Department of Pathology [S. Y. Z., A. J. P. K., M. S., S. M., T. G.] and Department of Surgical Oncology [E. R. S., J. A. R.], Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111 and Department of Medicine, University of California, San Diego, La Jolla, California 92093-0663 [T. N., D. A. C.]

Sixty-eight primary head and neck squamous cell carcinomas and nine head and neck squamous cell carcinoma cell lines were examined for mutations and homozygous deletions of the p16/CDKN2 gene. Homozygous deletions of the p16/CDKN2 gene were found in three lines, and a mutation was detected in another cell line. In contrast, none of the primary tumors showed homozygous deletions and 11 of 68 tumors had missense or nonsense base changes. Seven tumors contained somatic mutations. Five tumors, including one that also had a somatic mutation, had a probable polymorphism at codon 140 leading to an amino acid change from Ala to Thr. Three of these also contained an apparent polymorphism at codon 98, which did not lead to an amino acid change. The frequency of mutations and deletions detected differs markedly between cell lines (44%) and primary tumors (10%) suggesting that while p16/CDKN2 may play a role in tumorigenesis in some head and neck squamous cell carcinomas, inactivation of p16/CDKN2 probably occurs more frequently in cell lines as a result of adaptation to cell culture.

¹ This work was supported by NIH Grants CA53713 and CA06927.

² To whom requests for reprints should be addressed, at Fox Chase Cancer Center, Department of Pathology, 7701 Burholme Avenue, Philadelphia, PA 19111.

Received 8/ 5/94. Accepted 8/18/94.

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