Background. Chromosome Ip deletions are common in advanced neuroblastomas,
but the biological and clinical implications of this clonal rearrangement r
emain controversial. Previous studies of chromosome 1p loss of heterozygosi
ty (LOH) have been limited by analyses of relatively small number of tumors
derived from heterogeneously assessed and treated patient populations. The
refore, a strictly representative cohort of 288 Children's Cancer Group neu
roblastoma patients treated on the most recent phase III therapeutic trials
was identified. Procedure. Primary tumors from these patients were analyze
d for LOH at precisely mapped and highly informative Ip polymorphic loci lo
cated from 1p32 to 1p36.3 by multiplex PCR. Results, Ninety-three primary t
umor specimens (32%) had LOH at multiple 1p36 marker loci. All Ip deletions
overlapped the previously determined smallest region of overlap (SRO). One
tumor had a small terminal deletion completely within 1p36.31 allowing for
further refinement of the 1p36 SRO. We found no evidence to support an add
itional, nonoverlapping region of LOH within 1p32-36. We confirmed the stro
ng correlation of 1p36 LOH with MYCN amplification (P < 0.001), advanced di
sease stage (P < 0.001), and decreased both 3-year event-free survival and
overall survival probabilities (P < 0.001). When stratified for MYCN amplif
ication status or entered into a multivariate analysis, 1p36 LOH remained p
redictive for decreased event-free survival, but not overall survival proba
bility. Conclusions. These data support the hypothesis that inactivation of
a tumor suppressor gene within 1p36.3 is associated with an increased risk
for disease relapse. Med. Pediatr. Oncol. 36.32-36, 2001. (C) 2001 Wiley-L
iss. Inc.