Gene expression patterns in ependymomas correlate with tumor location, grade, and patient age

To elucidate the molecular events responsible for tumorigenesis and progression of ependymomas, we analyzed molecular alterations on the gene expression level in a series of newly diagnosed ependymal neoplasms (n = 39). To this aim, tumor RNA was hybridized to microarrays; comprising 2600 different genes with relevance to mitosis, cell-cycle control, oncogenesis, or apoptosis. For CLU, IGF-2, and RAF-1, which are apparent candidate genes because they had been previously described to be involved in tumorigenesis of other human malignancies, we found a high expression on the mRNA as well as the protein level We identified gene expression signatures for the differentiation of tumors with respect to location, grade, and patient age. Spinal ependymomas were characterized by high-expression levels of HOXB5, PLA2G, and CDKN2A and tumors in young patients (:516 years of age) by high-expression levels of LDHB and STAM Notably, we were able to classify supratentorial grade II and III tumors with 100% accuracy, whereas this did not apply for infratentorial ependymomas. The similar gene expression patterns of grade U and M infratentorial malignancies suggest that grade M tumors may develop through a secondary multistep transformation process involving genes that are related to cell proliferation (LDHA, cyclin B, ALMA) or tumor suppression (PTEN). In summary, our results provide new insight in the biochemical pathways particularly intriguing in the pathomechanism of ependymomas and suggest that this entity comprises molecularly distinct diseases.