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PTEN
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Interpretation 299
Tier 2
PTEN
Variants
PTEN any frameshift
PTEN any deletion
PTEN any missense
Primary Sites
Breast
Tumor Types
Invasive Ductal Carcinoma
Adenocarcinoma
Interpretation

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.

Citations
  1. Keniry M, et al. The role of PTEN signaling perturbations in cancer and in targeted therapy. Oncogene 2008;27(41):5477-85
  2. De Luca A, et al. The RAS/RAF/MEK/ERK and the PI3K/AKT signalling pathways: role in cancer pathogenesis and implications for therapeutic approaches. Expert Opin Ther Targets 2012;16 Suppl 2():S17-27
  3. Saal LH, et al. Recurrent gross mutations of the PTEN tumor suppressor gene in breast cancers with deficient DSB repair. Nat Genet 2008;40(1):102-7
  4. Saal LH, et al. Poor prognosis in carcinoma is associated with a gene expression signature of aberrant PTEN tumor suppressor pathway activity. Proc Natl Acad Sci U S A 2007;104(18):7564-9
  5. Tan MH, et al. Lifetime cancer risks in individuals with germline PTEN mutations. Clin Cancer Res 2012;18(2):400-7
Last updated: 2016-08-12 16:31:08 UTC
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When using PMKB, please cite: Huang et al., JAMIA 2017


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