Abnormalities of tumor suppressor genes P16 and P15 in primary maxillofacial squamous cell carcinomas

As members of the same gene family, tumor suppressor genes P16/CDKN2/INK4A and P15/INK4B have a high degree of structural and functional homology with both P16 and P15 proteins involved directly in the regulation of cell cycl es. However, the status of P16 and P15 genes in primary maxillofacial squam ous cell carcinomas (MSCC) has not been reported. Studies on abnormalities of these genes including homozygous deletion, methylation of the 5'CpG isla nds, and mutations were carried out in 65 primary MSCC with polymerase chai n reaction (PCR), methylation-specific PCR (MSP), PCR-SSCP (single-strand c onformation polymorphism), and DNA sequencing techniques. Of the 65 tumors, 22 (34%) were methylated; 7 (11%) displayed point mutations. The total fre quency of alteration of the P16 gene was 43% (28/65). The methylation rate of P15 was 12% (8/65). No homozygous deletion was found in either the P16 g ene or P15 gene. In all MSCC samples, almost half (49%) harbored an alterat ion of the P16 or P15 gene. The P16 gene was altered more frequently than P 15, and therefore is inactivated by methylation or mutation in a significan t proportion of MSCC. The P15 gene appeared to play a lesser role in tumori genesis of these tumors. (C) Elsevier Science Inc., 1999. All rights reserv ed.