P1.01-42 Whole-Exome Sequencing Identifies Novel Somatic Mutations Associated with Prognosis in Lung Cancer Metastatic to the Brain

Abstract

Lung cancer is the leading cause of cancer-related mortality in China and worldwide. Patients with lung cancer are the major origin of metastastatic brain tumor. Understanding the difference between primary lung lesion and brain metastases may contribute to the treatment strategy. To investigate the difference of somatic mutations in patients with non–small-cell lung cancer (NSCLC) and brain metastases. Whole-exome sequencing method were used in 13 paired lung cancer and brain metastasis samples from our institute. 6,318 SNVs and 56,686 mutation events in 3864 genes were observed in 13 paired lung cancer and brain metastasis samples. We identified 46 driven gene mutations which are most frequently related to lung cancer. Several lung cancer metastases associated genes (KMT2C, BAGE2 and FER1L4) and epigenetic factors (CHEK2P2, miR-4436A, miR-6077) were found as well. A mean of 3.1 driver mutation events per tumor with the dN/dS of 2.06 (95%CI: 1.73-2.4) in these samples which indicating a significant enrichment of the cancer driven mutations. Mutation spectrum analysis found that these samples have more similar transition (Ti) and transversion (Tv) profile, in which C->T transitions is more frequently seen in brain metastasis samples, while lung primary tumor have a higher frequency of C->A transversion. Furthermore we found the most important tumor onset and metastasis pathways in these samples, such as focal adhesion, PI3K-Akt signaling pathway and MAPK signaling pathway. What’s more, Glioma pathway were also identified which highly indicating the solid finding of the study.View Large Image Figure ViewerDownload Hi-res image Download (PPT) In summary, we conducted an exome-wide sequencing through pair wised lung primary and brain metastasis samples and identified some novel cancer and metastasis related mutation which provided potential biomarkers for prognosis and novel therapeutics.