Analysis of array-CGH data revealed that PTEN deficiency is coupled tightly with genomic amplification encompassing the NUAK2 locus, a finding strengthened by immunohistochemical evidence that phospho-Akt overexpression was correlated with NUAK2 expression in clinical specimens of acral melanoma.
Analysis of a melanoma tissue microarray showed loss of PTEN expression to predict for a lower overall survival, with a trend for even lower survival being seen when loss of fibronectin was included in the analysis.
The dCas9-VPR system increased PTEN expression in melanoma and TNBC cell lines, without transcriptional regulation at predicted off-target sgRNA binding sites.
Attenuation of ZEB2 expression activates the PI3K/AKT pathway, enhances cell transformation, and commonly occurs in human melanomas and other cancers expressing low PTEN levels.
As RAS can be a positive upstream regulator of PI3-K, it has been proposed that the loss of PTEN and the activation of RAS are redundant events in melanoma pathogenesis.
RAS itself is only infrequently mutated in melanoma although downstream of RAS lie BRAF on the mitogen-activated protein kinase pathway and PTEN on the protein kinase B/Akt pathway.
We found a high frequency of amino-acid-altering mutations in the melanomas and demonstrated that these mutations impaired PTEN function; UV damage plays a direct role in induction of mutations and in inactivation of the PTEN gene in XP melanomas including in situ, the earliest stage of melanoma.
Using the demethylation agent 5-aza-2'-deoxycytidine, reduced methylation and a corresponding increase in PTEN protein were observed in BLM melanoma cells, leading to reduced AKT activity in an in vitro kinase assay.
Somatic oncogenic mutation of BRAF coupled with inactivation of PTEN constitute a frequent combination of genomic alterations driving the development of human melanoma.
We thus sought to elucidate the prevalence of PTEN promoter methylation in melanoma specimens, its relationship to clinical features, and its impact on the outcome of patients with melanoma.
PTEN immunohistochemical loss, a common event in endometrioid-type endometrial carcinoma and associated with local immune suppression in melanoma, was not associated with PD-L1 expression or lymphocyte/macrophage infiltration of the tumor.