ALLELE LOSS IN WILMS-TUMORS OF CHROMOSOME ARMS 11Q, 16Q, AND 22Q CORRELATES WITH CLINICOPATHOLOGICAL PARAMETERS

An extended analysis for loss of heterozygosity (LOH) on eight chromos omes was conducted in a series of 82 Wilms tumors. Observed rates of a llele loss were: 9.5% (Ip), 5% (4q), 6% (6p), 3% (7p), 9.8% (11q), 28% (11 p 15), 13.4% (16q), 8.8% (18p), and 13.8% (229). Known regions of frequent allele loss on chromosome arms Ip, I I p 15, and 16q were an alyzed with a series of markers, but their size could not be narrowed down to smaller intervals, making any positional cloning effort diffic ult. In contrast to most previous studies, several tumors exhibited al lele loss for multiple chromosomes, suggesting an important role for g enome instability in a subset of tumors. Comparison with clinical data revealed a possible prognostic significance, especially for LOH on ch romosome arms I Iq and 229 with high frequencies of anaplastic tumors, tumor recurrence, and fatal outcome. Similarly, LOH 16q was associate d with anaplastic and recurrent tumors. These markers may be helpful i n the future for selecting high-risk tumors for modified therapeutic r egimens. (C) 1998 Wiley-Liss, Inc.