p73 gene transcripts in human brain tumors: overexpression and altered splicing in ependymomas

The p73 gene encodes a protein that shares structural and functional homolo gies with the p53 tumor suppressor protein. The p73 gene is monoallelically expressed in normal tissue, maps to chromosome 1p36 and is deleted in huma n neuroblastoma cell lines. Alternative splicing of exon 13 in p73 transcri pts generates two isoforms, p73 alpha and p73 beta, that differ in their ca rboxy-terminus and in their ability to form homotypic interactions. In this study, we investigated, in 129 human central nervous system tumors of vari ous histological types, the levels of p73 transcripts and the splicing char acteristics of p73 mRNA. Whereas p73 mRNA content was consistently low in m ost tumoral types, especially in meningiomas, some glioblastomas, medullobl astomas and metastases exhibited elevated p73 mRNA content. However, ependy momas expressed consistently high amounts of p73 mRNA, significantly differ ent from the other tumoral types. Whereas the short (p73 beta) isoform acco unted for 20-25% of the total p73 mRNA in most of the tumors, these splicin g characteristics were altered in ependymomas (only 9% of p73 beta) and in neurinomas (up to 53% of p73 beta). These observations suggest tissular or tumoral differences in the control of p73 gene transcription and alternativ e splicing, and raise the problem of the role of p73 isoforms in the contro l of tumor growth, particularly in ependymomas. (C) 1999 Elsevier Science I reland Ltd. All rights reserved.