AN INCREASED NM23H1 COPY NUMBER MAY BE A POOR PROGNOSTIC FACTOR-INDEPENDENT OF LOH ON 1P IN NEUROBLASTOMAS

In a study of 154 neuroblastomas, loss of heterozygosity (LOH) was obs erved on 1p (13%, 19/143), 11q (19%, 11/59), 14q (15%, 15/97), 17p (5% , 5/105) and 17q (17%, 9/52). We also found an increase in NM23H1 copy number in 14% (13/95) of neuroblastomas. All except one tumour with a n increased copy number stained positive with anti-NM23H1 monoclonal a ntibody. Event-free survival (EFS) was significantly shorter in 19 pat ients with LOH on 1p than in 128 without (41% vs 77% 4 year EFS, P=0.0 093), and in 13 patients with increased NM23H1 copy numbers than in 82 with normal copy numbers of the gene (61% vs 84% 4 year EFS, P=0.0103 ). LOH on 11q, 14q or 17q did not affect EFS. Most tumours with LOH on 1p, increased NM23H1 copy numbers or MYCN amplification occurred in p atients aged 12 months or more, those with advanced stage disease, and those who showed near diploidy or pseudodiploidy. However, LOH on 1p was found in only 1 of the 13 tumours with increased NM23H1 copy numbe rs, and MYCN amplification of four copies occurred in only one other s uch tumour. These findings suggest that the increased NM23H1 copy numb er may be a predictor for poor prognosis, independent of LOH on 1p, an d probably also of MYCN amplification.