Integrative Genomic Analysis Reveals a High Frequency of LKB1 Genetic Alteration in Chinese Lung Adenocarcinomas

Liver kinase B1 (LKB1) genetic alteration in lung cancer involves not only point mutations and small deletion of several base pairs but also exonic loss. However, most of recent studies in LKB1 gene status only focus on point mutations and small deletion, and thus may underestimate the actual frequency of LKB1 genetic alteration in lung cancer. Thus, an integrative analysis of LKB1 genetic alteration is timely and important for providing a better estimate for the incidence of genetic alterations in this important tumor suppressor gene. One hundred and seven lung adenocarcinomas with more than 70% tumor have been analyzed for mutation of LKB1 as well as LKB1 large deletions detection by using multiplex ligation-dependent probe amplification analysis. These samples were also analyzed for EGFR, KRAS, HER2, BRAF, ALK, ROS1, and RET status in stepwise method. Among 107 lung adenocarcinomas analyzed, 29 (27.1%) harbored LKB1 genetic alteration. Twenty-three (21.5%) harbored LKB1 large exonic deletions and eight (7.48%) had LKB1 points mutations, two samples harbored both LKB1 large exonic deletions and point mutations. Eighty-seven samples (81.31%) harbored known driver mutations and 20 samples (18.69%) had no identifiable driver mutations. A high rate of LKB1 genetic alteration in Chinese lung adenocarcinomas is revealed by the integrative analysis of point mutation and exonic deletion. Moreover, LKB1 genetic alterations are concurrent with EGFR, KRAS, HER2, and CD74-ROS fusions.