Expression level, allelic origin, and mutation analysis of the p73 gene in neuroblastoma tumors and cell lines.

Overview

The novel p73 gene is a structural and, in overexpression systems, functional p53 homologue. p73 resides on chromosome 1p36.33 within a commonly deleted region in neuroblastoma (NB) and other human tumors. To evaluate p73's candidacy for a NB suppressor, we analyzed 28 primary NB tumors, 14 NB cell lines, and 5 non-NB malignant pediatric tumors. We determined the level of p73 expression and its allelic origin and searched for mutations. Fifty-one different types of normal tissues all showed very low p73 expression. Although most NB tumors expressed p73 within the normal tissue range, wild-type p73 expression levels varied widely in NB and non-NB tumors and NB cell lines with increases up to 90-fold compared with normal tissues. Importantly, the p73 gene was biallelically expressed in five of six NB tumors and three of three normal 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 neuroblastoma development.