Untranslated region rewiring defines a novel class of oncogene fusions.

5' UTR-replacing gene fusions in cancer increase MET protein levels 5- to 10-fold without changing mRNA, revealing a new oncogenic mechanism.

• Why it matters: Understanding how gene regulation contributes to cancer progression is crucial, as traditional focus has been on protein-altering fusions. This work highlights a novel way that oncogenes can be overexpressed without altering their coding sequence, which may impact cancer diagnosis and treatment strategies.
• What they did: The authors analyzed over 200,000 cancer samples to identify fusions that replace the 5' UTR of MET, FGFR1, JAK2, and NTRK2, and demonstrated that these fusions increase protein abundance by affecting translational regulation, especially after irradiation.
• The result: This discovery of UTR rewiring as a mechanism of oncogene overexpression broadens understanding of cancer genomics and suggests new targets for precision oncology by focusing on untranslated region alterations.