The landscape of NFE2L2 alteration in Chinese solid tumor patients.

Abstract

e15126 Background: NFE2L2 encodes a transcription factor which is a member of a small family of basic leucine zipper (bZIP) proteins. NFE2L2 variations were detected in many tumors, such as lung cancer, esophageal cancer, renal cell carcinoma and other cancer types. The landscape of NFE2L2 gene in solid tumors of Chinese population has not been descripted. Methods: 3193 normal-paired samples from patients with solid tumors were analyzed using hybridization capture-based next generation sequencing, and alterations including single base substitution, short and long insertion/deletions, copy number variations, gene fusions and rearrangements. Results: NFE2L2 gene was altered in 2.0% (65 of 3193) of all solid tumors. The frequency of NFE2L2 variations was assessed in multiple cancer types, including lung cancer (33/1109), liver cancer (10/206), colorectal cancer (6/391), stomach cancer (3/227), cervical cancer (3/112), esophageal cancer (3/53), and other cancer types. A total of 54 variations of NFE2L2 were found, mainly in exon 2 (26/54), exon 5 (11/54), exon 3 (4/54) and exon 4 (2/54), no variation in exon 1. NFE2L2 D16G, D21H, R34_S40del, V36_E45del, F37_E45del, R42P, L48P, K53Tfs*2, L62P, E67Q and L76_E78delinsQ in exon 2 have not been reported before. In addition, we identified copy number amplifications of NFE2L2 in four patients, including three lung squamous cell carcinomas and one cervical squamous cell carcinoma patients. Furthermore, in our cohort, NFE2L2 mutation carriers also owned other actionable or driver mutation, the most frequent one was TP53 (71%), followed by PIK3CA (34%), MLL2 (28%), CDKN2A (31%), and ATR (25%). Analysis of co-mutation correlation of NFE2L2 showed that NFE2L2 variation was correlated with ATR, ACVR1B, TERC and Sox2 ( p<0.001). TERC and SOX2 were mainly copy number amplification at chromosome 3q36, and there is higher amplification frequency at 3q36 in squamous cell carcinoma. In TCGA cohort, the patients with NFE2L2 variations and 3q36 amplification had a longer median survival than those group without 3q36 amplification (63.59 vs 32.04 months, p = 0.0459). Conclusions: NFE2L2 deleterious mutations are highly diverse and present at low to moderate frequencies across many cancers. Our results revealed the potential targeted therapeutic strategies and prognostic analysis among NFE2L2 population with solid tumors should be considered in further study.