The landscape of NRG1 fusions based on NGS in Chinese solid tumor patients.

Abstract

e15073 Background: Neuregulin 1 gene ( NRG1) fusions are oncogenic in various tumor types and represent an emerging potential therapeutic target. In the previous reports, NRG1 fusions are overall rare (0.12%) in the Western population, being seen most frequently in NSCLCs. The incidence of NRG1 fusions in a variety of solid tumors based on NGS has been explored limitedly in Chinese patients. Methods: FFPE samples and matched peripheral blood were collected for NGS based 450 cancer genes panel assay and RNA panel assay.Somatic variants were analyzed following CAP/CLIA-certificated workflows, including Single Nucleotide Variant (SNV), Copy Number Variation (CNV), large insertion and deletions (Lindel) and gene rearrangements. Results: A total of 47 patients harboring NRG1 fusions and four of them were detected in RNA level. Non-small cell lung cancer (NSCLC) was the most common cancer type with the incidence of 0.19% (25/13089). The followed cancer types were bone sarcoma, breast carcinoma, pancreatic adenocarcinoma and colorectal carcinoma with the frequency of 0.30% (3/973), 0.16% (3/1850), 0.14% (3/2098) and 0.07% (3/4344) respectively. CD74 (10.1%), SLC34A2 (10.1%) and WRN (4.3%) represented the most common NRG1 fusion partners, other known partners contained CDH1, HMBOX1, ADAM5 and UNC5D. In total, 76.6% of the partners were novel partners, and the most common break points of NRG1 were intron5 and intron1. The 47 NRG1 fusion patients evenly distributed in female (49%) and male (51%), and 44.7% were at advanced stage (stage ≥ III). The median age was 57 years old (range, 8-86 years old) and the median TMB was 3.3 muts/Mb (range, 0-30.5). TP53 (48.9%), CDKN2A (14.9%) and ERBB2/FGFR1/MUC16/SMAD4 (12.8%) were the most common co-occurred mutated gene. In the alterations of ERBB2, 50% were amplifications and 2 patients were breast carcinoma. Only one patient showed ALK fusion and one showed FGFR1 fusion. Among all patients, 8.5% included p.G12X mutation of KRAS and 10.6% included alterations of EGFR with two L858R and two 19del mutations. Conclusions: This study revealed NRG1 fusions in approximately 0.19% of Chinese NSCLC tumor pts and presented the frequency of same common tumors. Also the genomic and clinical feature were analysed. NGS panel sequencing and OrigiFus algorithm showed the advantage of detecting NRG1 fusion and providing structure information of partners which could potentially guide more precise treatment options.