Biological and clinical role of p73 in neuroblastoma M. Romani a, * , G.P. Tonini a , B. Banelli a , G. Allemanni a , K. Mazzocco b , P. Scaruffi a , L. Boni c , M. Ponzoni d , G. Pagnan d , L. Raffaghello d , S. Ferrini e , M. Croce e , I. Casciano a a Laboratory of Tumor Genetics, Istituto Nazionale per la Ricerca sul Cancro (IST), Largo Rosanna Benzi 10, 16132 Genova, Italy b Neuroblastoma Research Laboratory, c/o CBA Largo Rosanna Benzi 10, 16132 Genova, Italy c Biomedical Technology Assessment, c/o CBA, Largo Rosanna Benzi 10, 16132 Genova, Italy d Differentiation Therapy Unit, Istituto G. Gaslini, Largo Gerolamo Gaslini 5, 16147 Genova, Italy e Laboratory of Immunopharmacology, Istituto Nazionale per la Ricerca sul Cancro (IST), Largo Rosanna Benzi 10, 16132 Genova, Italy Received 4 November 2002; accepted 11 November 2002 Abstract The p73 gene is a p53 homologue localized at 1p36.3, a chromosomal region frequently deleted in neuroblastoma. p73 was originally considered an oncosuppressor gene. However, it was soon realized that its mode of action did not resemble that of a classic anti-oncogene. The recent discovery of N-terminal truncated isoforms, with oncogenic properties, showed that p73 has a ‘two in one’ structure. Indeed, the full-length variants are strong inducers of apoptosis while the truncated isoforms inhibit the pro-apoptotic activity of p53 and of the full-length p73. This review summarizes some aspects of p73 biology with particular reference to its possible role in neuroblastoma. q 2003 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Neuroblastoma; p73; Apoptosis; Tumor suppressor gene; Methylation 1. Introduction The alteration of the 1p chromosomal region is a common feature of many human tumors [1]. In neuroblastoma (NB), somatic and constitutional 1pter deletions are observed in approximately 35% of the cases and the loss of heterozygosity of chromosome 1p independently predicts a decreased event-free survival probability. The smallest region of overlapping deletions in NB has been refined within 1p36.3, in a chromosome segment included between microsatellite markers D1S468 and D1S2666. The transfer of an intact chromosome 1p into NB cell lines reverts the transformed phenotype suggesting that this chromosome arm hosts at least one oncosuppressor gene. However, the infrequency of interstitial 1p deletions or of balanced translocations complicates the utilization of positional cloning techniques for the identification of genes relevant to the pathogenesis of NB or of the other tumors bearing chromosome 1p alterations. A considerable interest in NB research was recently raised by the discovery of p73,a p53 homologue that induces apoptosis and inhibits cell growth [2]. Since p73 maps at 1p36, it was originally 0304-3835/03/$ - see front matter q 2003 Elsevier Science Ireland Ltd. All rights reserved. doi:10.1016/S0304-3835(03)00092-2 Cancer Letters 197 (2003) 111–117 www.elsevier.com/locate/canlet * Corresponding author. Tel./fax: þ 39-10-573-7501. E-mail address: massimo.romani@istge.it (M. Romani).