PMID- 16447252 OWN - NLM STAT- MEDLINE DCOM- 20060609 LR - 20060403 IS - 0021-9541 (Print) IS - 0021-9541 (Linking) VI - 207 IP - 3 DP - 2006 Jun TI - TP53 and p16INK4A, but not H-KI-Ras, are involved in tumorigenesis and progression of pleomorphic adenomas. PG - 654-9 AB - The putative role of TP53 and p16(INK4A) 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 in 4% (1/28) and 7% (2/28) of PAs, respectively. Only 20% (1/5) of carcinomas screened displayed mutations in K-Ras. p16(INK4A) 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 p16(INK4A) promoter methylation, but not alterations in the H-Ras and K-Ras genes, might be involved in the malignant progression of PA into carcinoma. CI - Copyright 2006 Wiley-Liss, Inc. FAU - Augello, Claudia AU - Augello C AD - Department of Oncology, Universita of Palermo, Palermo, Italy. FAU - Gregorio, Valter AU - Gregorio V FAU - Bazan, Viviana AU - Bazan V FAU - Cammareri, Patrizia AU - Cammareri P FAU - Agnese, Valentina AU - Agnese V FAU - Cascio, Sandra AU - Cascio S FAU - Corsale, Simona AU - Corsale S FAU - Calo, Valentina AU - Calo V FAU - Gullo, Arianna AU - Gullo A FAU - Passantino, Rita AU - Passantino R FAU - Gargano, Grazia AU - Gargano G FAU - Bruno, Loredana AU - Bruno L FAU - Rinaldi, Gaetana AU - Rinaldi G FAU - Morello, Vincenza AU - Morello V FAU - Gerbino, Aldo AU - Gerbino A FAU - Tomasino, Rosa Maria AU - Tomasino RM FAU - Macaluso, Marcella AU - Macaluso M FAU - Surmacz, Eva AU - Surmacz E FAU - Russo, Antonio AU - Russo A LA - eng PT - Journal Article PL - United States TA - J Cell Physiol JT - Journal of cellular physiology JID - 0050222 RN - 0 (Cyclin-Dependent Kinase Inhibitor p16) RN - 0 (Tumor Suppressor Protein p53) RN - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras)) SB - IM MH - Adenoma/*genetics/metabolism/*pathology MH - Base Sequence MH - Cell Transformation, Neoplastic/*genetics/metabolism/*pathology MH - Cyclin-Dependent Kinase Inhibitor p16/*genetics/metabolism MH - Disease Progression MH - Epigenesis, Genetic/genetics MH - Genotype MH - Humans MH - Methylation MH - Mutation/genetics MH - Proto-Oncogene Proteins p21(ras)/genetics MH - Tumor Suppressor Protein p53/*genetics EDAT- 2006/02/01 09:00 MHDA- 2006/06/10 09:00 CRDT- 2006/02/01 09:00 PHST- 2006/02/01 09:00 [pubmed] PHST- 2006/06/10 09:00 [medline] PHST- 2006/02/01 09:00 [entrez] AID - 10.1002/jcp.20601 [doi] PST - ppublish SO - J Cell Physiol. 2006 Jun;207(3):654-9. doi: 10.1002/jcp.20601.