Abstract 614: Clinical implications of NRG1 fusion in invasive mucinous adenocarcinoma of the lung

Background: We investigated the clinical implications of NRG1 fusion, a newly identified oncogenic rearrangement, in surgically resected invasive mucinous adenocarcinoma (IMA) of the lung. Patients and Methods: We performed RNA sequencing on 7 lung adenocarcinomas that had no known driver oncogenes and identified a novel fusion, SLC3A2-NRG1 in a case of IMA. The newly detected NRG1 fusion was verified in an IMA cohort of 59 cases using reverse transcription polymerase chain reaction (RT-PCR), direct sequencing and fluorescence in situ hybridization (FISH) analysis. Targeted caner panel sequencing and RT-PCR were performed to identify the possible coexistence of NRG1 fusions and other genetic alterations. Results: After screening 59 IMA, we found a total of 16 NRG1 fusions (13 SLC3A2-NRG1 and 3 CD74-NRG1). Among the 16 cases with NRG1 fusion, concurrent KRAS codon 12 mutations were found in 10 cases. We also found concurrent NRAS Q61L mutation and EML4-ALK fusion in additional two cases with NRG1 fusion. When comparing survival according to the presence of an NRG1 fusion, patients harboring NRG1 fusion showed inferior overall survival (OS) compared to those without NRG1 fusion (median 51.9 months [mo] vs. not reached [NR], P = 0.019). They also showed a trend toward shorter disease-free survival (DFS) (median 21.9 vs. 79.4 mo, P = 0.113). In the stage I IMA, patients with NRG1 fusion showed significantly inferior OS (median 48.1 mo vs. NR, P = 0.009) and DFS (median 18.9 vs. 91.1 mo, P = 0.013) compared to those without NRG1 fusion. Conclusion: NRG1 fusion is an important prognostic factor in IMA and should be considered a novel therapeutic target for IMA. Citation Format: Ji-Youn Han, Yeon-Su Lee, Dong Hoon Lee, Dong Wan Hong, Seung Hyun Hong, Jung-Ah Hwang, Byung Il Lee, Hye Jin You, Dong Hoon Shin, Geon Kook Lee. Clinical implications of NRG1 fusion in invasive mucinous adenocarcinoma of the lung. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 614. doi:10.1158/1538-7445.AM2015-614