Tumor suppressor gene p16 (CDKN2A) mutation status and promoter inactivation in head and neck cancer

The p16(INK4A) (CDKN2A/MTS1) putative tumor suppressor gene encodes a cycli n dependent kinase inhibitor which plays an important role in the regulatio n of the G1/S phase cell cycle checkpoint. A high frequency of various p16 gene alterations were consequently observed in many primary tumors. P16 can be inactivated by different mechanisms: i) homozygous deletion, ii) methyl ation of the promoter region or iii) point mutation. In order to investigat e p16 alterations in head and neck cancer (HNC) we analyzed 70 primary tumo rs of the larynx, pharynx and oral cavity including their corresponding nor mal mucosa for mutation inactivation by. direct sequencing exon 2. We detec ted only one so far undescribed transversion G to T at position 322 (Asp108 Tyr) and a known polymorphism (Ala148Thr) in five casks. The methylation st atus of the p16 promoter region was analyzed by an improved highly sensitiv e methylation-specific PCR protocol. PIG methylation inactivation was found in 16 of 55 cases (29%). Our data indicate that p16 point mutations in HNC are less frequent, but inactivation by methylation of the promoter region could be involved in genesis and progression of HNC.