OVEREXPRESSION OF THE ROS1 GENE IN PRIMARY HUMAN GLIOMAS MAY CONTRIBUTE TO MALIGNANT PROGRESSION

Gliomas are malignant brain tumors thought to arise through multi-step tumorigenesis, involving both the activation of oncogenes and the los s of tumor suppressor genes. The ros1 gene encodes a proto-oncogenic p rotein which has been implicated, by in vitro studies, in the pathogen esis of several types of cancer, including gliomas. Northern blot anal ysis revealed expression of ros1 mRNA in 3 (30%) of 10 primary glioma specimens. In situ hybridization localized ros1 mRNA transcripts to GF AP positive tumor cells and pericytes around capillaries. Immunohistoc hemistry using an antibody specific for ros1 demonstrated strong posit ivity amongst neoplastic glial cells in the same glioma samples. No ro s1 mRNA or protein was detected in 5 normal brain specimens. These dat a provide the first evidence for the overexpression of ros1 mRNA and p rotein in primary human gliomas, and are consistent with a proposed on cogenic role of ros1 in these tumors.