As reported in Clinical Cancer Research, Nakaoku and colleagues identified oncogene fusions that function as driver mutations in KRAS wild-type invasive mucinous adenocarcinoma of the lung.
Whole-transcriptome sequencing of 32 invasive mucinous adenocarcinomas, including 27 without KRAS mutations, identified several oncogenic fusions that occurred only in the absence of KRAS mutations, including CD74-NRG1, EZR-ERBB4, and TRIM24-BRAF fusions. NRG1 fusions were present in 18% of KRAS-negative adenocarcinomas.
Functional analyses of the fusion gene products showed that the CD74-NRG1 fusion activated HER2:HER3 signaling and that EZR-ERBB4 and TRIM24-BRAF fusions constitutively activated the ERBB4 and BRAF kinases, respectively. Signaling pathway activation and fusion-induced anchorage-independent growth and tumorigenicity of NIH3T3 cells expressing these fusions were reduced by treatment with tyrosine kinase inhibitors.
The investigators concluded, “Oncogenic fusions act as driver mutations in [invasive mucinous adenocarcinomas] without KRAS mutations, and thus represent promising therapeutic targets for the treatment of such [disease].” ■
Nakaoku T, et al: Clin Cancer Res. April 11, 2014 (early release online).
