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PTEN
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Interpretation 2293
Tier 2
PTEN
Variants
PTEN R15I
Primary Sites
Colon
Tumor Types
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. Approximately 20-30% of colorectal carcinomas involve biallelic inactivation of PTEN through a combination of genetic and epigenetic mechanisms. The R15I missense mutation falls within the PIP2 binding motif in the phosphatase domain of PTEN, which involves residues 6-15. PTEN R15I has been show to result in loss of phosphatase activity in vitro. Clinical trials using PI3K-beta inhibitor are available for patients with 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. Mighell TL, Evans-Dutson S, O'Roak BJ. A Saturation Mutagenesis Approach to Understanding PTEN Lipid Phosphatase Activity and Genotype-Phenotype Relationships. Am J Hum Genet. 2018 May 3;102(5):943-955.
  3. Molinari F, Frattini M. Functions and Regulation of the PTEN Gene in Colorectal Cancer. Front Oncol. 2014 Jan 16;3:326.
  4. Kato H, Kato S, Kumabe T, Sonoda Y, Yoshimoto T, Kato S, Han SY, Suzuki T,
  5. Shibata H, Kanamaru R, Ishioka C. Functional evaluation of p53 and PTEN gene
  6. mutations in gliomas. Clin Cancer Res. 2000 Oct;6(10):3937-43.
  7. Gil A, Rodriguez-Escudero I, Stumpf M, Molina M, Cid VJ, Pulido R. A functional dissection of PTEN N-terminus: implications in PTEN subcellular targeting and tumor suppressor activity. PLoS One. 2015 Apr 15;10(4):e0119287.
Last updated: 2019-01-22 18:32:23 UTC
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When using PMKB, please cite: Huang et al., JAMIA 2017


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