PEDIATRIC BRAIN-TUMORS EXPRESS MULTIPLE RECEPTOR TYROSINE KINASES INCLUDING NOVEL CELL-ADHESION KINASES

We have used the polymerase chain reaction to clone and characterize g rowth factor receptor tyrosine kinases (RTKs) expressed in 3 pathologi cally distinct pediatric brain tumors, an anaplastic ependymoma, a gli oblastoma multiforme and a primitive neuroectodermal tumor (PNET). The se neoplasms are presumed to be derived from embryonic neuroepithelial precursor cells of the central nervous system. This cloning demonstra ted expression of 24 distinct kinase genes: 16 receptor type kinases a nd 8 nonreceptor type kinases. The expression of 6 receptors, includin g Hek2, IRR, Ryk, FGFR3, and 2 members of the newly identified cell ad hesion kinase receptor family, DDR and TKT, in such tumors has not bee n reported previously. Northern analysis of mRNA levels revealed DDR e xpression in 6 of 7 pediatric brain tumors including an ependymoma, PN ET, glioblastoma and astrocytoma, and also in an adult pheochromocytom a. Thus, the DDR cell adhesion kinase may be widely expressed in pedia tric brain tumors. Also, PCR cloning may be an effective procedure for characterizing RTKs in clinical tissue samples and revealing the expr ession of novel RTK species.