Also known as proto-oncogene tyrosine-protein kinase ROS, ROS1 is an orphan receptor tyrosine kinase that belongs to the insulin receptor family. It is highly expressed in the brain, and in primary gliomas. Like other tyrosine kinases, ROS1 phosphorylates a wide range of substrates, including STAT3, VAV3, PTPN11, AKT1, MAPK1, MAPK3, and IRS1, resulting in activation of signaling pathways involved in cell growth, differentiation, proliferation, and survival.

 

ROS1 is a transmembrane protein with tyrosine kinase activity with putative function as a growth or differentiation factor receptor. ROS1 expression is limited in normal tissues to occasional staining cerebellum, stomach, small intestine, colon and kidney. Rearrangements of the ROS1 proto-oncogene was originally detected in glioblastoma and cholangiocarcinoma. ROS1 fusion partners include CD74, SLC34A2 and SDC4, leading to oncogenic transformation. ROS1 neoplastic transformation is widely studied in non-small cell lung cancer (NSCLC). While ROS1 is undetectable in the normal lung, studies have described ROS1 rearrangements in 1-2% of NSCLC by FISH. Recent reports have demonstrated strong correlation between ROS1 immunoreactivity with FISH positivity