Neuroblastomas with chromosome 11q loss and single copy MYCN comprise a biologically distinct group of tumours with adverse prognosis

Neuroblastoma is a heterogeneous tumour and its effective clinical manageme nt is dependent on accurate prognostic evaluation. In approximately 25% of patients amplification of the MYCN oncogene is known to be associated with a poor outcome. In order to identify additional molecular markers with prog nostic potential in non-MYCN-amplified neuroblastomas, we looked for a corr elation between clinical outcome and loss of heterozygosity (LOH) on four c hromosomes that frequently show alteration in neuroblastoma (chromosomes 3, 4, 11 and 14). Chromosome 11q loss (with frequent parallel loss of chromos omes 3p, 4p and/or 14q) was found exclusively in tumours; without MYCN ampl ification and was significantly associated with poor event-free survival. T he 2-year event-free survival rate for 11q LOH cases was 30%, compared to 3 4% for MYCN-amplified cases and 100% for cases without these abnormalities. While 11q LOH was associated predominantly with advanced-stage disease, 2 cases with low-stage disease and 11q LOH both suffered relapses. We conclud e that chromosome 11q loss defines a biologically distinct group of tumours without MYCN amplification that appear to have potential for aggressive me tastatic growth. Thus this genetic alteration may be an important new progn ostic marker in neuroblastoma. (C) 2001 Cancer Research Campaign.