Truncating mutations of PPM1D are found in blood DNA samples of lung cancer patients.

ABSTRACT:

Background

PPM1D (WIP1) negatively regulates by dephosphorylation many proteins including p53 tumour suppressor. The truncating mutations (nonsense and frameshift) in exon 6 of PPM1D were found recently in blood cells of patients with breast, ovarian or colorectal cancer. These mutants code for gain-of-function PPM1D with retained phosphatase activity. Their significance in carcinogenesis is unknown.

Methods

The exon 6 of PPM1D was sequenced in blood DNA of 543 non-small-cell lung cancer patients (NSCLC). The functional significance of selected PPM1D alterations (Arg458X, Lys469Glu) was compared with the wild-type gene and examined by recombinant DNA techniques, immunoblotting and luciferase reporter assays.

Results

The frameshift mutations were found in five NSCLC pa

SUBMITTER: Zajkowicz A 

PROVIDER: S-EPMC4366904 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature