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. Somatic mutations in PTEN have been found in 4-8% of non-small cell carcinomas (NSCLC) including adenocarcinomas and squamous cell carcinomas. 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. The PTENI101T has been observed in a variety of cancer types, most frequently gliomas, and has been predicted to be pathogenic. However, one study identified the PTEN I101T variant in 1 out of 172 patients with germline PTEN mutations.
- Keniry M, et al. The role of PTEN signaling perturbations in cancer and in targeted therapy. Oncogene 2008;27(41):5477-85
- Hollander MC et al. PTEN loss in the continuum of common cancers, rare syndromes and mouse models. Nat Rev Cancer. 2011 Apr;11(4):289-301. doi: 10.1038/nrc3037.
- Martin L. Sos et al. PTEN Loss Contributes to Erlotinib Resistance in EGFR-Mutant Lung Cancer by Activation of Akt and EGFR. Cancer research 69.8 (2009): 3256--3261. PMC. Web. 27 Aug. 2015.
- Wong CW, Or PMY, Wang Y, Li L, Li J, Yan M, Cao Y, Luk HM, Tong TMF, Leslie NR, Lo IF, Choy KW, Chan AML. Identification of a PTEN mutation with reduced protein stability, phosphatase activity, and nuclear localization in Hong Kong patients with autistic features, neurodevelopmental delays, and macrocephaly. Autism Res. 2018 Aug;11(8):1098-1109.