GOPC-ROS1 fusion protein (GOPC-ROS1)

The GOPC-ROS1 fusion protein is formed by the in-frame fusion of the N-terminal exons of GOPC (typically exons 1–7 or 1–4) to the C-terminal kinase domain of ROS1 (exons 35–43), resulting in a constitutively active receptor tyrosine kinase chimera[1][2][4]. This fusion acts as an oncogenic driver in a small subset of gliomas (particularly infantile hemispheric glioma but also in adult glioblastoma and pilocytic astrocytoma), colorectal cancer, and other rare solid tumors. Detection of the GOPC-ROS1 fusion identifies patients who may benefit from therapy with ROS1 tyrosine kinase inhibitors. The fusion protein drives aberrant cell signaling by ligand-independent activation of the ROS1 kinase, activating pathways that promote cell proliferation and survival, and is now considered a clinically actionable therapeutic target in tumors harboring this alteration[1][2][3][4]. The fusion event produces a protein with different subcellular localization and regulatory properties compared to wild-type ROS1. GOPC-ROS1 fusions are rare but have outsized relevance due to the existence of targeted therapies and implication as a key biomarker for precision oncology approaches[1][2]. ENSG00000282218 appears to be an Ensembl transcript or fusion event identifier rather than a separate canonical gene, and the primary therapeutic relevance is through the characterization and targeting of the fusion protein product[4].

Other names

GOPC-ROS1 readthroughGOPC:ROS1GOPC-ROS1 fusion

Inhibition of the constitutively active ROS1 kinase domain of the fusion protein, blocking downstream signaling pathways such as MAPK, PI3K-AKT-mTOR, and JAK-STAT3, thereby reducing cell proliferation and inducing tumor regression[2].