Abstract 1083P
Background
The tumor suppressor gene neurofibromin 1 (NF1) is a major regulator of the RAS-MAPK pathway and NF1 mutations have been reported in various cancers including non–small-cell lung cancer (NSCLC). NF1 mutations define a unique population of NSCLC. But best treatment patterns in the NF1 mutation group is unclear. Herein, we assessed the molecular characteristics, tumor mutational burden (TMB), microsatellite instability (MSI) and PD-L1 expression in Chinese NF1-mutated NSCLC to explore the possibility of Immunotherapy.
Methods
In this study, we retrospectively analyzed NF1 mutations, TMB and MSI using next-generation sequencing (NGS). PD-L1 status was determined by VENTANA PD-L1 (SP263) Assay. For the purposes of this study, we only analyzed loss-of-function (LOF) and predicted loss of function mutations (PLOF) in the NF1 gene.
Results
A total of 202 LOF/PLOF NF1 mutations were found, and 28 patients carried double NF1- LOF/PLOF mutations. 183 unique NF1 nucleotide variants were identified in 174 patients. Variants in NF1 included nonsense mutations (n=90), frameshift mutations (n=61), splice site mutations (n=42), and missense mutations (n=9). Mutations are spread throughout all exons of the NF1 gene. 56 NF1 variants indentified in 52 tumors occurred with other driver mutations/fusions (EGFR (22); KRAS (19); MET (5); ROS1 (3); ALK (2); EGFR&KRAS(1); BRAF(0);ERBB2(0); RET(0)). The media TMB was significantly higher in patients harboring NF1 mutations compared with their wild-type counterparts. (8.1 vs.2.2, P < .001). No cases had an MSI-H status in the NF1 mutation cohort. 51 patients in the NF1 mutations cohort and 1326 patients in the wild-type NF1 cohort could be evaluated for PD-L1 tumor cell expression. PD-L1 tumor cell expression in the NF1 mutations cohort was significantly higher than in the wild-type NF1 cohort. (P < .001).
Conclusions
The prevalence of LOF/PLOF NF1 mutations was 2.2% (174/7632) in Chinese NSCLC patients. NF1 mutations do exist with concurrent oncogenic alterations but the majority of NF1 mutations in NSCLC occur independently. NF1 mutation was associated with higher TMB and higher PD-L1 tumor cell expression. Immune Checkpoint Inhibitors may be considered as an option for patients with NSCLC harboring NF1 mutations.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.