A new study has detected NRG1 fusions in a small percentage of multiple solid tumors types.1 These gene fusions could represent novel oncogenic drivers, according to study researchers.

The researchers conducted a retrospective analysis looking at more than 21,000 tumor specimens after RNA sequencing using the ArcherDx fusion assay (Archer FusionPlex Solid Tumor® panel) to detect NRG1 fusions.

Of the analyzed tumors, 41 (0.2%) harbored a NRG1 fusion. “Of the 41 NRG1 fusions identified, 34 were in-frame, 3 were out-of-frame variants of unknown significance, and 4 were translated variants,” the authors wrote.

The greatest incidence of NRG1 fusions occurred in non-small cell lung cancer (25 of 41); however, the researchers noted that this represented only a very small percentage (0.3%) of lung cancer cases tested.

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NRG1 fusions were also identified in samples from gallbladder cancer (0.5% of tested gallbladder cases), renal cell carcinoma (0.5%), bladder cancer (0.1%), ovarian cancer (0.4%), pancreatic cancer (0.5%), breast cancer (0.2%), neuroendocrine tumor, sarcoma (0.2%), and colorectal cancer (0.1%).

A number of fusion partners were also identified across tumor types. In NSCLC, the most common fusion partner was CD74; other partners detected in NSCLC included SDC4, SLC3A2, TNC, MDK, ATP1B1, and 6 other types of fusions.

NRG1 fusions were mutually exclusive from other common oncogenic alterations including EGFR, KRAS, ALK, ROS1, and RET.

Reference

  1. Jonna S, Feldman RA, Swensen J, et al. Detection of NRG1 gene fusions in solid tumors [published online April 15, 2019]. Clin Cancer Res. doi: 10.1158/1078-0432.CCR-19-0160