PTEN is an obligate haplo-insufficient tumor suppressor gene and is mutated in a large number of cancers. It encodes a phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase. It negatively regulates intracellular levels of phosphatidylinositol-3,4,5-trisphosphate in cells and functions as a tumor suppressor by negatively regulating AKT/mTOR signaling pathway. Cancer-associated alterations in this gene often result in loss of PTEN protein and upregulation of the PI3K/AKT/mTOR pathway. PTEN mutations have been reported in 15% of anaplastic thyroid cancer. Germline mutations of PTEN lead to inherited hamartoma and Cowden syndrome. Patients with Cowden syndrome have an increased risk of developing epithelial thyroid cancer, follicular carcinoma being the most common, of up to 10% compared to <1% in the general population. Clinical trials using PI3K-beta inhibitor are available for patients with PTEN-deficient tumors.

Somatic mutations in PTEN have been found in 4-8% of non-small cell carcinomas (NSCLC) including adenocarcinomas and squamous cell carcinomas. PTEN is a tumor suppressor gene, and loss of PTEN results in upregulation of the PI3K/ AKT pathway. Loss of PTEN is most commonly due to promoter hypermethylation, while homozygous deletion and nonsense mutations with loss of heterozygosity (LOH) may also occur. PTEN mutations may occur in multiple exons. In preclinical studies, PTEN loss is associated with decreased sensitivity of EGFR mutant lung tumors to EGFR TKIs. Clinical trials assessing the efficacy of PI3K inhibitors in PTEN loss are being explored.

PTEN is an obligate haplo-insufficient tumor suppressor gene and is commonly mutated in a large number of cancers. It negatively regulates intracellular levels of Phosphatidylinositol (3,4,5)-trisphosphate (PIP3) in cells and functions as a tumor suppressor by negatively regulating AKT/mTOR signaling pathway. Mono- and bi-allelic loss of PTEN is found in approximately 40-50% and 5% of breast cancers, respectively. It has been reported to occur in BRCA1-associated basal-like breast cancer. Germline mutations in PTEN are also responsible for Cowden disease, a rare autosomal dominant multiple-hamartoma syndrome. In one study, germline mutations of PTEN have been reported to be associated with 85% lifetime risk of breast cancer in patients with PTEN hamartoma tumor syndrome. Aberrant PTEN pathway is associated with metastases and poor prognosis in breast cancer. It also predicts poor response to trastuzumab. There are ongoing clinical trials investigating anti-tumor activity of PI3K-beta inhibitor in PTEN deficient tumors.

PTEN is an obligate haplo-insufficient tumor suppressor gene and is commonly mutated in a large number of cancers. It negatively regulates intracellular levels of Phosphatidylinositol (3,4,5)-trisphosphate (PIP3) in cells and functions as a tumor suppressor by negatively regulating AKT/mTOR signaling pathway. PTEN mutations have been reported in up to 19% of gastric cancers. Germline mutations in PTEN are also responsible for Cowden disease, a rare autosomal dominant multiple-hamartoma syndrome. Patients with Cowden disease can have gastric polyps, but a possible association with gastric cancer needs further study. Inactivation of PTEN is shown to be closely associated with tumor progression and metastases. Clinical trials using PI3K-beta inhibitor are available for patients with PTEN-deficient tumors.

PTEN is a lipid and protein phosphatase that negatively regulates the PI3K/AKT/mTOR pathway. Cancer-associated alterations in this gene often result in loss of PTEN protein and upregulation of the PI3K/AKT/mTOR pathway. PTEN mutations have been reported in ~2% of head and neck squamous cell carcinomas and 15% of anaplastic thyroid carcinomas. Germline mutations of PTEN lead to inherited hamartoma and Cowden syndrome. This particular variant M134I has been reported as a likely pathogenic germline variant (ClinVar, https://preview.ncbi.nlm.nih.gov/clinvar/variation/428267/) and has also been reported as a somatic variant. Clinical trials using PI3K-beta inhibitor are available for patients with PTEN-deficient tumors.