Loss of MKK3 and MK2 Copy Numbers in Non-Small Cell Lung Cancer

Abstract

Identification of genetic alterations in members of the p38 mitogen-activated protein kinase (MAPK) pathway is important as these proteins have dynamic roles in tumor progression and may serve as potential therapeutic targets in cancer. We analyzed tumor and non-tumorous lung tissue of 233 non-small cell lung cancer (NSCLC) patients for the presence of copy number alterations (CNAs) in the MAPK kinase 3 (MKK3) and MAPK-activated kinase 2 (MK2) genes. We report frequent CNAs in MKK3 and MK2 genes in NSCLC. Copy number losses were detected in 31% of NSCLC tumors (odds ratio: 7.08, 95% confidence interval: 3.2-15.6, P<0.001) for the MKK3 gene and in 28% of tumors for the MK2 gene (odds ratio: 3.68, 95% confidence interval: 1.9-7.2, P<0.001). Several of the non-tumorous tissues showed an elevated MKK3 copy number, with a concurrent loss of this in 89% of the paired tumors. MKK3 gene deletions were significantly more frequent in squamous and large cell carcinoma than in adenocarcinoma. These data demonstrate a novel loss of MKK3 and MK2 genomic copy numbers in NSCLC tumors, and suggest these genes as interesting therapeutic candidates in NSCLC.

Keywords: MK2; MKK3; copy number alterations; non-small cell lung cancer.; p38 MAPK.

Figure 1

MKK3 and MK2 copy number status in NSCLC. Percentage of copy number atlterations (CNAs) in (A) MKK3 and (C) MK2 genes in lung tumors and non-tumorous tissues. Distribution of (B) MKK3 and (D) MK2 gene CNAs in NSCLC of different histology. Copy number loss was defined as copy number ≤1.55; whereas, gain was defined as copy number ≥2.45.