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Study Takes First Comprehensive Look at Methylation Patterns in Salivary Gland Tumors

July 20, 2010

Methylation pattern for tumor suppressor gene Timp3Darwin had his finch beaks, the paleontologist Edward Drinker Cope had his teeth, and in the latter half of the 20th century a few dedicated researchers had salivary glands as their favorite model to study natural selection. The latter studies of more than 300 mammalian species showed that salivary glands, because they are non-essential to life, had 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. In the May issue of PLoS ONE, 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 four 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 three of the four tumor types. But 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.

  • Quantitative Methylation Profiles for Multiple Tumor Suppressor Gene Promoters in Salivary Gland Tumors, Durr Ml, Mydlarz KW,Shao C, Zahurak ML, Chuang AY, Hoque MO, Westra WH, Liegeois NJ, Califano JA, Sidransky D, and Ha PK.  PLoS ONE, May 26,2010;5(5):e10828.

 

 

 

 

 

 

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This page last updated: February 26, 2014