P70.09 NOTCH1 Mutations in East Asian Patients With Non-Small-Cell Lung Cancer

Abstract

NOTCH1 is a class I transmembrane (TM) protein which directly transduce extracellular signal into gene expression changes which function as ligand activated transcription factors. Interaction of the receptor with D like and Jagged ligands expressed on the surface of neighboring cells initiate NOTCH1 signal. The aim of this study is to investigate mutations and prognosis of non-small cell lung cancer (NSCLC) harboring NOTCH1 mutations. A total of 976 patients with non-small-cell lung cancer were recruited between July 2012 and December 2018. The status of NOTCH1 mutations and other genes were detected by next generation sequencing. NOTCH1 gene mutation rate was 4.41% (43/976) in non-small cell lung cancer, including Y1738N(1 patient), A2256V(1 patient), M2318T(1 patient), P1257L(1 patient), S1140Afs*39(1 patient), N1460I(1 patient), V874G(1 patient), M2363I(1 patient), R1758H(1 patient), V2007M(1 patient), N41I(1 patient), N2248I(1 patient), R1662Q(1 patient), C768Y(1 patient), P1731L(2 patients), L1593P(1 patient), R79L(1 patient), D573A plus D1880N(1 patient), A2256V(1 patient), Y202S(1 patient), D388N(1 patient), A1418T(1 patient), C1363G(1 patient), V354E(1 patient), T445M(1 patient), A208T(1 patient) (1 patient), R2104H(1 patient), E1294*(1 patient), R1991H(2 patients), R203H(1 patient), T2132M(1 patient), G925Afs*254(1 patient), Y1738N(1 patient), P460Q(1 patient), R1991Pfs*9(1 patient), T1079Pfs*23(1 patient), V1307I(1 patient), M2318T(1 patient), G1437W(1 patient), E455K(1 patient) and V1750M, and median overall survival (OS) for these patients was 26.0 months. Among them, all patients were NOTCH1 gene with co-occurring mutations. Briefly, patients with (n=6) or without (n=37) co-occurring EGFR mutations had a median OS of 26.0 months and 16.0 months respectively (P=0.26); patients with (n=31) or without (n=12) co-occurring TP53 mutations had a median OS of 26.0 months and not up to now respectively (P=0.60); patients with (n=11) or without (n=32) co-occurring KRAS mutations had a median OS of not up to now and 16.0 months respectively (P=0.08); patients with (n=9) or without (n=34) co-occurring NF1 mutations had a median OS of not up to now and 26.0 months respectively (P=0.97). EGFR, TP53, KRAS, NF1 gene accompanied may have less correlation with NOTCH1 mutation in NSCLC patients. We report different mutations than those previously reported, which emphasizes the importance of personalized medicine that could be empowered by the use of bioinformatics tools in the diagnostic process and therapeutic approaches.