A coding single-nucleotide polymorphism in lysine demethylase KDM4A associates with increased sensitivity to mTOR inhibitors.

ABSTRACT:

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SNPs occur within chromatin-modulating factors; however, little is known about how these variants within the coding sequence affect cancer progression or treatment. Therefore, there is a need to establish their biochemical and/or molecular contribution, their use in subclassifying patients, and their impact on therapeutic response. In this report, we demonstrate that coding SNP-A482 within the lysine tridemethylase gene KDM4A/JMJD2A has different allelic frequencies across ethnic populations, associates with differential outcome in patients with non-small cell lung cancer (NSCLC), and promotes KDM4A protein turnover. Using an unbiased drug screen against 87 preclinical and clinical compounds, we demonstrate that homozygous SNP-A482 cells have increased mTOR inhibitor sen

SUBMITTER: Van Rechem C 

PROVIDER: S-EPMC4355226 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature