TP53 and p16INK4A, but not H-KI-Ras, are involved in tumorigenesis and progression of pleomorphic adenomas.
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.
Augello
Claudia
C
Department of Oncology, Università of Palermo, Palermo, Italy.
Gregorio
Valter
V
Bazan
Viviana
V
Cammareri
Patrizia
P
Agnese
Valentina
V
Cascio
Sandra
S
Corsale
Simona
S
Calò
Valentina
V
Gullo
Arianna
A
Passantino
Rita
R
Gargano
Grazia
G
Bruno
Loredana
L
Rinaldi
Gaetana
G
Morello
Vincenza
V
Gerbino
Aldo
A
Tomasino
Rosa Maria
RM
Macaluso
Marcella
M
Surmacz
Eva
E
Russo
Antonio
A
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*
D019941:Cyclin-Dependent Kinase Inhibitor p16; D016159:Tumor Suppressor Protein p53; D016283:Proto-Oncogene Proteins p21(ras)