The role of PTEN as a cancer biomarker

The phosphatase and tensin homologue, PTEN, was identified in 1997 and later found to be frequently disrupted in multiple sporadic tumour types and targeted by germline mutations in patients with cancer predisposition syndromes such as Cowden disease [1]. The principal catalytic function of PTEN is to dephosphorylate phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5) P3), which is a potent activator of 3-phosphoinositidedependent kinase (PDK) and AKT. As a consequence, loss of PTEN function leads to increased levels of PtdIns(3,4,5)P3 and activation of the phosphoinositide 3-kinase (PI3K)–AKT pathway which stimulates cell growth and survival. Additionally, recent data demonstrate that nuclear PTEN has now been demonstrated to maintain genomic stability through regulation of RAD51, a key protein involved in double-strand break (DSB) repair and stabilisation of replication fork during replication stress [2]. These distinct functions of PTEN and associated cancer predisposing mutations, has caused great interest in PTEN as a cancer biomarker.