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402652 | New Interpretation | 01/22/2019 1:32 PM |
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Tier 2InterpretationPTEN 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.
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Citations- Keniry M, et al. The role of PTEN signaling perturbations in cancer and in targeted therapy. Oncogene 2008;27(41):5477-85
- 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.
- Molinari F, Frattini M. Functions and Regulation of the PTEN Gene in Colorectal Cancer. Front Oncol. 2014 Jan 16;3:326.
- Kato H, Kato S, Kumabe T, Sonoda Y, Yoshimoto T, Kato S, Han SY, Suzuki T,
- Shibata H, Kanamaru R, Ishioka C. Functional evaluation of p53 and PTEN gene
- mutations in gliomas. Clin Cancer Res. 2000 Oct;6(10):3937-43.
- 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.
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Last updated: 2019-01-22 18:32:23 UTC
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