
<ArticleTitle>Inactivation of the <prot>p14</prot>(<prot>ARF</prot>), <prot>p15</prot>(<prot>INK4B</prot>) and <prot>p16</prot>(<prot>INK4A</prot>) genes is a frequent event in human oral squamous cell carcinomas.</ArticleTitle>
<AbstractText>The <prot>p14</prot>(<prot>ARF</prot>), <prot>p15</prot>(<prot>INK4B</prot>) and <prot>p16</prot>(<prot>INK4A</prot>) genes were localized to 9p21, where genetic alterations have been reported frequently in various human tumors. We performed a molecular analysis of the mechanism of inactivation in cell lines and 32 oral squamous cell carcinoma (OSCC), using deletion screening, PCR-SSCP, methylation-specific-PCR and cycle sequencing. We detected homozygous deletion of <prot><prot>p14</prot>(<prot>ARF</prot>)-1Ebeta</prot> in 9 (26.5%), of <prot>p15</prot>(<prot>INK4B</prot>) in one (3.1%), and of <prot>p16</prot>(<prot>INK4A</prot>) in 22 (56.3%) tumor samples. Three mutations were detected in the <prot>p16</prot>(<prot>INK4A</prot>) genes. We detected aberrant methylation of the <prot>p14</prot>(<prot>ARF</prot>) genes in 14 (43.8%), of the <prot>p15</prot>(<prot>INK4B</prot>) gene in 9 (28.1%), and of the <prot>p16</prot>(<prot>INK4A</prot>) gene in 16 (50.0%) tumor samples. Altogether, 87.5% of the samples harbored at least one of the alterations in the <prot>p14</prot>(<prot>ARF</prot>), <prot>p15</prot>(<prot>INK4B</prot>), and <prot>p16</prot>(<prot>INK4A</prot>) genes, indicating that the frequent inactivation of these genes may be an important mechanism during OSCC development.</AbstractText>
