Simultaneous analysis of , , and gene fusions by NanoString in Brazilian lung adenocarcinoma patients.

Background: Gene fusions have been successfully employed as therapeutic targets for lung adenocarcinoma. However, tissue availability for molecular testing of multiples alterations is frequently unfeasible. We aimed to detect the presence of and rearrangements by a RNA-based single assay in Brazilian lung adenocarcinomas and to associate with clinicopathological features and genetic ancestry.

Methods: From a FFPE series of 444 molecularly characterized lung adenocarcinomas, 253 wild-type cases were eligible for gene rearrangement analysis. Following RNA isolation, and rearrangements were simultaneously analyzed employing the ElementsXT Custom panel (NanoString Technologies). Rearrangements were further associated with clinicopathological features and genetic ancestry of the patients.

Results: The NanoString platform was performed in subset of 142 cases. Gene fusion results were conclusive for 94.4% (n=134) cases (failure rate =5.6%). rearrangements were observed in 21 out of 134 cases, and associated with younger, never smokers, metastatic disease, and metastases in the central nervous system. and fusions were detected in two and one out of 134 cases, respectively. Genetic ancestry was not associated with gene fusions. Overall, considering all cases for which a molecular analysis was conclusive (), fusions frequency was observed in 6.5% (21/325), in 0.6% (2/325), and ROS1 in 0.3% (1/325).

Conclusions: This study successfully used a RNA-based single assay for the simultaneous analysis of , , and fusions employing routine biopsies from Brazilian patients lung adenocarcinoma allowing an extensive molecular testing for actionable rearrangements contributing to guide clinical strategies.