Pathogenesis

Germline mutations in PTEN, a gene mapped to chromosome 10q22-23, have been found in most cases of CS (4). PTEN consists of nine exons spanning 100 kb of DNA and encodes a dual specificity phosphatase, which acts as a tumor-suppressor gene. Tissues capable of proliferation, such as epidermis, thyroid, and breast epithelium, and the oral and gastrointestinal mucosa are affected by disruption of this gene. PTEN mutations have also been observed in patients with Bannayan-Riley-Ruvalcaba (BRR) syndrome (characterized by hamartomatous polyps of the small and large intestine), and Lhermitte-Duclos disease (LDD), characterized by hamartomatous overgrowth of the cerebellar ganglion cells. This region was also found to be frequently deleted in thyroid tumors, and somatic mutations spanning this region are commonly found in glioblastoma, breast cancers (in association with CS), and advanced prostate cancer.

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