EXPRESSION LEVEL, ALLELIC ORIGIN, AND MUTATION ANALYSIS OF THE P73 GENE IN NEUROBLASTOMA TUMORS AND CELL-LINES

The novel p73 gene is a structural and, in overexpression systems, fun ctional p53 homologue. p73 resides on chromosome 1p36.33 within a comm only deleted region in neuroblastoma (NE) and other human tumors. To e valuate p73's candidacy for a NE suppressor, we analyzed 28 primary NE tumors, 14 NE cell lines, and 5 non-NE malignant pediatric tumors, We determined the level of p73 expression and its allelic origin and sea rched for mutations, Fifty-one different types of normal tissues all s howed very low p73 expression, Although most NE tumors expressed p73 w ithin the normal tissue range, wild-type p73 expression levels varied widely in NE and non-NE tumors and NE cell lines with increases up to 90-fold compared with normal tissues, Importantly, the p73 gene was bi allelically expressed in five of six WE tumors and three of three norm al tissues. Mutation analysis of the entire open reading frame of the gene in 16 tumors (including all 6 highly expressing tumors) revealed four polymorphic sites, but no mutations. Collectively, our data argue that p73 is unlikely to be a suppressor gene inactivated during neuro blastoma development.