A CONSTITUTIONAL BWS-RELATED T(11-16) CHROMOSOME-TRANSLOCATION OCCURRING IN THE SAME REGION OF CHROMOSOME-16 IMPLICATED IN WILMS-TUMORS

Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth disorder with a varying spectrum of clinical manifestations including macroglos sia, omphalocele, hemihypertrophy, and a predisposition to a subset of embryonal tumors, most frequently Wilms' tumor (WT). A variety of cyt ogenetic, generic linkage, and molecular mapping data implicate a gene or genes on chromosome band 11p15.5 in BWS and its related rumors, Ho wever, some families with BWS do not show linkage to 11p15, and other alterations have been found in Wilms' rumors as well. One such alterat ion is loss of heterozygosity (LOH) for chromosome arm 16q. Here we ha ve analyzed a balanced t(11;16)(p15;q13) chromosomal translation assoc iated with the BWS phenotype and mapped the breakpoint positions for b oth chromosomes 11 and 16 by using somatic cell hybrids and polymorphi c markers, The chromosome 11 breakpoint was found to lie distal to the D11S12 locus, but proximal to TH on 11p15.5, a region shown previousl y co contain ocher BWS-related chromosomal events. The chromosome 16 b reakpoint was distal to D16S290 in 16q13, but proximal to loci D16S265 , D16S267, and D16S164 in band 16q21. This area encompasses the region of LOH occurring through mitotic recombination in sporadic WT. This r aises interesting possibilities for the generic and epigenetic involve ment of both chromosomal regions (11p15 and 16q13) in the pathogenesis of BWS and Wilms' tumor. (C) 1995 Wiley-Liss, Inc.