The putative role of TP53 and p16INK4A tumor suppressor genes and Ras oncogenes in the development and progression of salivary
gland neoplasias was studied in 28 cases of pleomorphic adenomas (PA), 4 cases of cystic adenocarcinomas, and 1 case of
carcinoma ex-PA. Genetic and epigenetic alterations in the above genes were analyzed by Polymerase Chain Reaction/Single
Strand Conformational Polymorphism (PCR/SSCP) and sequencing and by Methylation Specific-PCR (MS-PCR). Mutations in TP53
were found in 14% (4/28) of PAs and in 60% (3/5) of carcinomas. Mutations in H-Ras and K-Ras were identified in4%(1/28) and7%
(2/28) of PAs, respectively. Only 20% (1/5) of carcinomas screened displayed mutations in K-Ras. p16INK4A promoter
hypermethylation was found in 14% (4/28) of PAs and 100% (5/5) carcinomas. All genetic and epigenetic alterations were detected
exclusively in the epithelial and transitional tumor components, and were absent in the mesenchymal parts. Our analysis suggests
that TP53 mutations and p16INK4A promoter methylation, but not alterations in the H-Ras and K-Ras genes, might be involved in the
malignant progression of PA into carcinoma. J. Cell. Physiol. 207: 654–659, 2006. 2006 Wiley-Liss, Inc