Author Affiliations: The Sidney Kimmel Comprehensive Cancer Center, the Johns Hopkins University School of Medicine, Baltimore, Maryland.
The phosphatase and tensin homolog gene (PTEN) (RefSeq NM_000314) is a tumor suppressor located on the human chromosome 10q arm and is an important mediator of carcinogenesis in a variety of human malignancies.1 By the strictest definition, a tumor suppressor is a gene whose loss confers an increased lifetime risk of developing tumors. The most illustrative examples of genes that fulfill this criterion are those associated with familial cancer syndromes whereby heritable inactivation of 1 allele and subsequent increased tumor risk is passed along to each generation in an autosomal-dominant fashion.2 Using this as a framework, PTEN is a bona fide tumor suppressor gene in that heritable germline mutations have been described in Cowden syndrome (CS), giving rise to a number of human tumors and cancers, most notably thyroid and breast cancers.3 As is the paradigm of tumor suppressor genes, affected patients with CS inherit 1 mutant inactive copy of PTEN from either parent, and the ensuing loss of the second allele results in tumor formation with subsequent genetic events that eventually lead to cancer. Although there are notable exceptions to this model, most heritable cancer syndromes are believed to adhere to this pattern.
Jelovac D, Park BH. PTEN Promoter Silencing and Cowden Syndrome: The Role of Epigenetic Regulation of KILLIN. JAMA. 2010;304(24):2744–2745. doi:10.1001/jama.2010.1863
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