O. Takeda et al., THERE MAY BE 2 TUMOR-SUPPRESSOR GENES ON CHROMOSOME ARM IP CLOSELY ASSOCIATED WITH BIOLOGICALLY DISTINCT SUBTYPES OF NEUROBLASTOMA, Genes, chromosomes & cancer, 10(1), 1994, pp. 30-39
We studied loss of heterozygosity (LOH) on chromosome arm 1p in 108 ne
uroblastomas using 14 polymorphic DNA markers. One-hundred and four tu
mors with one or more informative loci; 21 (20%) of the 104 tumors sho
wed LOH on 1p, and were classified into three groups on the basis of i
nterstitial or terminal allelic loss, and presence or absence of LOH o
n 1p. Seven of the 21 tumors showed an interstitial deletion which enc
ompassed a small region in 1p36 (group A), and the other 14 showed a t
erminal deletion which encompassed the region from 1pter to 1p32 (grou
p B). Eighty-three tumors without LOH on 1p were classified as group C
. The group A patients were mostly less than 12 months of age (6/7), w
ere frequently found by a mass screening program for infants (5/7), ha
d a tumor of non-adrenal origin, and rarely progressed to stage IV (1/
7). Most group B patients were 12 months or older (11/14), were found
clinically (11/14), had tumors of adrenal origin, and progressed to st
age IV (10/14). Analysis of biologic characteristics in group C tumors
suggested that they may comprise group A and B tumors. While all grou
p A tumors were in the triploid range (3n) (4/4), most group B tumors
were diploid (2n) or tetraploid (4n) (7/10). MYCN amplification was fo
und in 8 group B tumors, but in none of group A tumors. Event-free sur
vivals of groups A, B, and C patients at 3 years were 86, 49, and 74%,
respectively (P = 0.0287). These findings suggest that there may be t
wo tumor suppressor genes on 1p which are closely associated with two
biologically distinct subtypes of neuroblastoma. (C) 1994 Wiley-Liss,
Inc.