Augello Claudia, Gregorio Valter, Bazan Viviana, Cammareri Patrizia, Agnese Valentina, Cascio Sandra, Corsale Simona, Calò Valentina, Gullo Arianna, Passantino Rita, Gargano Grazia, Bruno Loredana, Rinaldi Gaetana, Morello Vincenza, Gerbino Aldo, Tomasino Rosa Maria, Macaluso Marcella, Surmacz Eva, Russo Antonio
Department of Oncology, Università of Palermo, Palermo, Italy.
J Cell Physiol. 2006 Jun;207(3):654-9. doi: 10.1002/jcp.20601.
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.
在28例多形性腺瘤（PA）、4例囊腺癌和1例PA恶变癌中，研究了TP53和p16（INK4A）肿瘤抑制基因以及Ras癌基因在涎腺肿瘤发生发展中的假定作用。通过聚合酶链反应/单链构象多态性（PCR/SSCP）、测序以及甲基化特异性PCR（MS-PCR）分析上述基因的遗传和表观遗传改变。在14%（4/28）的PA和60%（3/5）的癌中发现TP53突变。在PA中，H-Ras和K-Ras突变分别在4%（1/28）和7%（2/28）中被鉴定出。在筛查的癌中，仅20%（1/5）显示K-Ras突变。在14%（4/28）的PA和100%（5/5）的癌中发现p16（INK4A）启动子高甲基化。所有遗传和表观遗传改变仅在上皮和过渡性肿瘤成分中检测到，间叶部分未出现。我们的分析表明，TP53突变和p16（INK4A）启动子甲基化，而非H-Ras和K-Ras基因的改变，可能参与了PA向癌的恶性进展。
