CHARACTERIZATION OF A PINEAL REGION MALIGNANT RHABDOID TUMOR - TOWARDS UNDERSTANDING BRAIN-TUMOR CELL INVASION

The malignant rhabdoid tumor (MRT) of the central nervous system is a highly aggressive neoplasm of early infancy which is characterized by brain invasion and widespread dissemination along cerebrospinal fluid pathways. As the process of tumor invasion is mediated in part by the elaboration of proteases and protease inhibitors by tumor cells, we so ught to determine the expression of the type-IV collagenases and their inhibitors (tissue inhibitors of metalloproteases, TIMPs) in an MRT f rom the pineal region of a 9-month-old male. In addition, as only a fe w reports exist concerning the cytogenetic abnormalities in MRTs, the cytogenetic features of this MRT were examined. When placed into tissu e culture, the MRT grew vigorously in early passages. The cytogenetic analysis of the cells in passage one revealed a near diploid karyotype with some metaphases demonstrating monosomy 22. Northern analysis of type-IV collagenase transcripts revealed that the MRT expressed the hi ghest levels of the 72- and 92-kD type-IV collagenase transcripts of a ny pediatric brain tumor examined. However, the MRT did not express an y significant amounts of the TIMP-1 or TIMP-2 transcripts. By in situ hybridization analysis, the MRT demonstrated marked intratumoral expre ssion of the type-IV collagenase but not TIMP transcripts. The results from this study suggest that this particular MRT may be a highly inva sive brain tumor, at least in part on the basis of overexpression of t he type-IV collagenases relative to the TIMPs.