Methylation Patterns in Salivary Gland Tumors

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  • #10842
    DrAnil
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    Registered On: 12/11/2011
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    Methylation Patterns in Salivary Gland Tumors

    Studies of more than 300 mammalian species have shown that salivary glands, because they are nonessential to life, have a greater capacity to evolve than the body’s vital organs. In other words, the evolutionary parameters of the liver or kidneys are limited to support their essential functions. That’s not the case with salivary glands. Their rapid adaptation served as a primary means for many spe­cies to settle into new environments, outcompete their rivals, and fill ecological niches. It explains, for example, why a snake’s bite can be deadly, a giraffe readily chews thorns, and a feeding tick can go undetected for many hours. The above also provides a broad biological framework to consider while thinking about the genetics of human salivary glands. 
         National Institute of Den­tal and Craniofacial Research (NIDCR) grantees and colleagues add some thought-provoking data with the results of the first extensive study of DNA methylation patterns in healthy salivary glands and 4 salivary tumor types (pleomorphic adenoma, adenoid cystic carcinoma, mucoepidermoid carcinoma, and salivary duct carcinoma). DNA methylation occurs when a methyl group attaches often to the promoter region of a gene. The methyl tag alters the gene’s ability to interact with needed transcription regulators, thereby turning off the gene. Although DNA methylation often occurs naturally to make one inherited gene dominant over another, tumor cells often co-opt the methylation process early in their development to shut down growth-inhibiting tu­mor suppressor genes and enable their aberrant behavior. In the study, the scientists evaluated the methylation patterns of 19 tumor suppressor genes in a total of 95 tissue samples (17 normal, 78 from either be­nign or malignant tumors). The researchers discovered surprising variation in the frequency and quantity of methylation among the different tumor types. The same held true for the healthy tissue. Indeed, the average level of methylation in the panel of tumor suppressor genes was comparable in healthy tissue and 2 of the 4 tumor types. However, the study did produce a few leads. They found that several tumor suppressor genes were associated with malignant salivary gland tumors, especially for salivary duct carcinoma. Further study is needed to pin down or rule out these leads.

    #15841
    Drsumitra
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    Registered On: 06/10/2011
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      No methylation was detected in the normal tissues. Methylation occurred in 9 of 23 (39.1%) benign tumors; 3 (25.0%) pleomorphic adenomas and 6 (66.7%) Warthin’s tumors at the MGMT, DAPK, or RASSF1 genes. Methylation occurred in 33 of 79 (41.8%) malignant tumors; 8 (30.8%) adenoid cystic carcinomas, 6 (33.3%) mucoepidermoid carcinomas, 6 (42.9%) acinic cell carcinomas, and 13 (62.0%) salivary duct carcinomas. RASSF1 and RARβ2 represented 75.8% of methylation events occurring most frequently in salivary duct and acinic cell carcinomas. Overall, we found no significant correlation between protein expression and methylation status of individual genes, but observed low or absent protein expression in several methylated tumors. Significant correlations were found between methylation and aggressive malignant phenotypes (P = 0.0004) and age (P = 0.05).

     

    Conclusions: (a) Benign and malignant salivary tumors differed in the frequency and pattern of gene methylation; (b) high-grade carcinomas were significantly methylated compared with low-grade phenotypes; (c) RASSF1 and RARβ2 were highly methylated in malignant tumors and can be targeted for therapy; and (d) methylation pattern may serve as a diagnostic and biological marker in assessing these tumors.

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