The role of PTEN, a phosphatase gene, in inherited and sporadic nonmedullary thyroid tumors.

Abstract

PTEN/MMACI/TEP1, a tumor suppressor gene located on 10q23.3, encodes an almost ubiquitously expressed dual-specificity phosphatase. Germline mutations in PTEN have been found in the majority of cases of sporadic and familial Cowden syndrome (CS), an autosomal dominant inherited cancer syndrome characterised by multiple hamartomas and benign and malignant disease of the thyroid and breast. Interestingly, germline mutations in PTEN have also been found in about 50% of a related but distinct disorder, Bannayan-Ruvalcaba-Riley syndrome (BRR), which is characterised by neonatal-onset macrocephaly, mental retardation, Hashimoto's thyroiditis, lipomatosis, haemangiomas, hamartomatous polyps, and pigmented macules of the glans penis. Somatic PTEN mutation has been described to a greater or lesser extent in various benign and malignant tumor types. Somatic deletions have been described in follicular adenomas of the thyroid and papillary thyroid carcinomas.