|Tumor(s)||Squamous Cell Carcinoma|
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. This particular variant is likely to be oncogenic. 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.
Alphy Rose-James et al. Molecular Markers with Predictive and Prognostic Relevance in Lung Cancer. Lung Cancer International, vol. 2012, Article ID 729532, 12 pages, 2012. doi:10.1155/2012/729532
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.
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.
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