Germline PIK3CA and AKT1 mutations in Cowden and Cowden-like syndromes.

[cowden syndrome]

Cowden syndrome (CS ) is a difficult-to -recognize multiple hamartoma syndrome with high risks of breast , thyroid , and other cancers . Germline mutations in PTEN on 10 q 23 were found to cause 85 % of CS when accrued from tertiary academic centers , but prospective accrual from the community over the last 12 years has revealed a 25 % PTEN mutation frequency . PTEN is the phosphatase that has been implicated in a heritable cancer syndrome and subsequently in multiple sporadic cancers and developmental processes . PTEN antagonizes the AKT 1 /PI 3 K signaling pathway and has roles in cell cycle , migration , cell polarity , and apoptosis . We report that 8 of 91 (8 .8 %) unrelated CS individuals without germline PTEN mutations carried 10 germline PIK 3 CA mutations (7 missense , 1 nonsense , and 2 indels ) and 2 (2 .2 %) AKT 1 mutations . These mutations result in significantly increased P-Thr 308 -AKT and increased cellular PIP 3 . Our observations suggest that PIK 3 CA and AKT 1 are CS susceptibility genes .

Diseases
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Diseases presenting "but prospective accrual from the community over the last 12 years has revealed a 25%" symptom

cowden syndrome

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