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Novel Regions of Allelic Imbalance Identified by Genome-wide Analysis of Neuroblastoma¹

Departments of Pathology [J. M., S. O., L. C., W. G.] and Pediatrics [N-K. V. C.), Memorial Sloan-Kettering Cancer Center, New York, New York 10021

Several nonrandom chromosomal abnormalities have been associated withneuroblastoma (NB). However, the relationship of each genetic event to the clinical course of disease is not firmly established. We have performed a genome-wide allelic scan of NB to identify regions with frequent allelic imbalance (AI) and correlate the allelotype with clinical features of disease. Nineteen tumors from patients across the spectrum of NB were used. Genome-wide allelotype was performed using 169 fluorescently labeled microsatellite markers from the Weber 9a human screening set (Research Genetics, Huntsville, AL) and 48 independent markers for high-density analysis of selected regions. Eleven chromosomal regions had AI in >25% of tumors including loci known previously to be frequently altered such as 1p36 (10 of 19; 52%), 2p (9 of 19; 47%), 17q (8 of 19; 42%), 11q23 (8 of 19; 42%), 14q32 (7 of 19; 37%), 19q (6 of 19; 31%), 7q (6 of 19; 31%), 9p21 (5 of 19; 26%), and three novel regions of frequent AI at 10p11-p15 (7 of 19; 40%), 12q24.1 (5 of 19; 26%), and 8qcen–q24 (5 of 19; 26%). AI of four regions (8q, 10p, 19q, and 12q) allowed the distinction of two genetic groups that matched clinical significant subgroups of NB. AI at 12q24 and 19q13 was found exclusively in high-risk local-regional tumors, whereas AI at 10p11 and 8q appeared to be specific for stage 4 tumors with MCYN amplification. Spontaneously remitting or quiescent tumors were intact at all of the regions described above.

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