title: TP53 and p16INK4A, but not H-KI-Ras, are involved in tumorigenesis and progression of pleomorphic adenomas.
abstract: 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.
authors.affiliation: Department of Oncology, Università of Palermo, Palermo, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Augello
authors.forename: Valter
authors.initials: V
authors.lastname: Gregorio
authors.forename: Viviana
authors.initials: V
authors.lastname: Bazan
authors.forename: Patrizia
authors.initials: P
authors.lastname: Cammareri
authors.forename: Valentina
authors.initials: V
authors.lastname: Agnese
authors.forename: Sandra
authors.initials: S
authors.lastname: Cascio
authors.forename: Simona
authors.initials: S
authors.lastname: Corsale
authors.forename: Valentina
authors.initials: V
authors.lastname: Calò
authors.forename: Arianna
authors.initials: A
authors.lastname: Gullo
authors.forename: Rita
authors.initials: R
authors.lastname: Passantino
authors.forename: Grazia
authors.initials: G
authors.lastname: Gargano
authors.forename: Loredana
authors.initials: L
authors.lastname: Bruno
authors.forename: Gaetana
authors.initials: G
authors.lastname: Rinaldi
authors.forename: Vincenza
authors.initials: V
authors.lastname: Morello
authors.forename: Aldo
authors.initials: A
authors.lastname: Gerbino
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Tomasino
authors.forename: Marcella
authors.initials: M
authors.lastname: Macaluso
authors.forename: Eva
authors.initials: E
authors.lastname: Surmacz
authors.forename: Antonio
authors.initials: A
authors.lastname: Russo
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D044127:Epigenesis, Genetic / Q000235:genetics; D005838:Genotype; D006801:Humans; D008745:Methylation; D009154:Mutation / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D016159:Tumor Suppressor Protein p53; D016283:Proto-Oncogene Proteins p21(ras)