Abstract 1144: Detection of a novel ALK fusion variant in lung adenocarcinoma using a comprehensive genomic analysis

Abstract

Abstract Background: Anaplastic lymphoma kinase (ALK) is a tyrosine kinase that is constitutively activated in a subset of non-small cell lung cancer (NSCLC), mainly as a result of chromosomal translocation. In ALK-rearranged NSCLC, the growth of tumors is strongly addicted to ALK activity, and suppression of ALK is a potent therapeutic strategy. To date, 6 known fusion partners of ALK onco-kinase have been reported in NSCLC, although the sensitivity to ALK inhibitor according to fusion variant except for EML4-ALK is still unclear. In this study, we reviewed clinical trial samples analyzed by comprehensive genomic profiling approach to detect unknown actionable ALK rearrangements. Materials and methods: We reviewed gene alteration and expression profile of clinical samples in preliminary molecular studies from the ongoing BATTLE-2, phase II clinical trial of targeted drugs in chemo-refractory NSCLC. Results: In 187 NSCLC samples, 3 samples harbored ALK fusion gene: 2 EML4-ALK and 1 novel ALK fusion variant PRKAR1A-ALK in a lung adenocarcinoma of male former smoker patient. The ALK gene expression levels of ALK-rearranged samples were significantly higher compared to other samples. Interestingly, the patient harboring PRKAR1A-ALK was treated with ALK inhibitor crizotinib and showed long time stable disease. Conclusions: Our findings suggest that PRKAR1A-ALK fusion could be a novel oncogenic driver in lung adenocarcinoma and an indicator of ALK inhibitor response. (NHI-NCI CA155196; 2P50CA070907-16A1) Citation Format: Kazuhiko Shien, Dennis Ruder, Ecaterina E. Ileana, Vassiliki A. Papadimitrakopoulou, Garrett M. Frampton, Carmen Behrens, Neda Kalhor, J. Jack Lee, Ximing Tang, Roy S. Herbst, Ignacio I. Wistuba, Julie G. Izzo. Detection of a novel ALK fusion variant in lung adenocarcinoma using a comprehensive genomic analysis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1144.