THERE MAY BE 2 TUMOR-SUPPRESSOR GENES ON CHROMOSOME ARM IP CLOSELY ASSOCIATED WITH BIOLOGICALLY DISTINCT SUBTYPES OF NEUROBLASTOMA

We studied loss of heterozygosity (LOH) on chromosome arm 1p in 108 neuroblastomas using 14 polymorphic DNA markers. One-hundred and four tumors with one or more informative loci; 21 (20%) of the 104 tumors showed LOH on 1p, and were classified into three groups on the basis of interstitial or terminal allelic loss, and presence or absence of LOH on 1p. Seven of the 21 tumors showed an interstitial deletion which encompassed a small region in 1p36 (group A), and the other 14 showed a terminal deletion which encompassed the region from 1pter to 1p32 (group 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), were frequently found by a mass screening program for infants (5/7), had 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 stage IV (10/14). Analysis of biologic characteristics in group C tumors suggested that they may comprise group A and B tumors. While all group 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 found in 8 group B tumors, but in none of group A tumors. Event-free survivals 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 two tumor suppressor genes on 1p which are closely associated with two biologically distinct subtypes of neuroblastoma. (C) 1994 Wiley-Liss, Inc.