Abstract 3411: Genomic profiling of non-small cell lung cancer in Xuanwei, Yunnan Province
Authors: Guo Gang , Shou Tao , Li Gaofeng , Peng Hao , Zhao Juan , Guo Honglin , Zhang Lin , Shi Yunfei 
Published: August 2019

Abstract
Background
Xuanwei, a rural county, is located in the northeast of Yunnan Province, China. According to a national retrospective survey on cancer mortality during 1973-1975, the highest mortality rate of lung cancer in Xuanwei was 5.3 times higher than that in rural areas nationwide. Age standardized mortality rates (ASMR) of lung cancer were 23.14/105 and 4.34/105 in Xuanwei and rural areas in China respectively. Characterization of genomic alterations(GAs) that drive patients (pts) disease development is critical in cancer management. However, the comprehensive genomic features of pts with non-small cell lung cancer (NSCLC) in Xuanwei have not been well understood.
Methods:
Next generation sequencing (NGS) targeting 37 lung cancer related driver genes was performed on FFPE and matched blood samples that collected from 85 NSCLC pts in Xuanwei. The pts included 50 males (59%) and 35 females (41%) with a median age of 54 years (range 36-78). GAs including single nucleotide variations (SNV), short and long insertions and deletions (Indel), copy number variations (CNV), and gene rearrangements were analyzed.
Results:
The histological subtypes of our cohort included LUAD(n=68, 80%), LUSC(n=9, 10.6%) and others(n=8, 9.4%).The most common GAs detected were TP53 (56%), EGFR (46%), KRAS mutation (25%), APC (8%), PIK3CA (8%), CDKN2A (7%), PTEN (6%), ALK (5%), CDK4 (5%), MTOR (5%), NTRK3 (5%) and PDGFRA (5%). In total, 74.1% of the pts had one or more actionable GAs. PI3K/mTOR pathway alterations including PTEN, MTOR,TSC1/2 and PIK3CA mutations were detected in 23.5% of the pts. Compared with OrigiMed unpublished data from larger Chinese NSCLC pts (EGFR 47.6%, ALK fusion 8.3%, KRAS 12.3%, n=1200), we identified similar frequency of EGFR mutation, while we found significant higher frequency of KRAS mutation(25%, n=85, P &lt;0.001) and lower incidence of ALK fusion (1.2%, n=85, P =0.025) in Xuanwei cohort.
Comparing to OrigiMed unpublished data(as above), comprehensive genomic profiling (CGP) identified unique EGFR mutation profile in Xuanwei cohort that G719X occurred much more frequently (43.6% vs. 5.15%, P &lt;0.001).
43.6%(17/39) EGFR-mutant pts harbored the uncommon mutation G719X, which could be identified alone (8%) or combined with other EGFR mutations (35.6%), the distribution of combined G719X mutations are G719X+S768I (15.4%),G719X+E709A(5.1%),G719X+G779C(5.1%),G719X+L838V(2.5%),G719X+L861Q(2.5%),G719X+S768I+N1107D(2.5%),G719X+T790M+V651L(2.5%).
Conclusions:
Comparing to the large cohort of Chinese pts with NSCLC, we identified higher mutation frequency of KRAS (P &lt;0.001) and lower frequency of ALK fusion (P =0.025) in Xuanwei cohort. EGFR uncommon mutation G719X were identified in 43.6% of EGFR-mutant pts, but only accounted for 5.15% of EGFR-mutant pts in large Chinese NSCLC cohort. Therefore, the NGS based target sequencing assay revealed a unique pattern of driver gene mutations in Xuanwei cohort.
Citation Format: Gang Guo, Tao Shou, Gaofeng Li, Hao Peng, Juan Zhao, Honglin Guo, Lin Zhang, Yunfei Shi. Genomic profiling of non-small cell lung cancer in Xuanwei, Yunnan Province [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3411.