MOLECULAR SUBLOCALIZATION AND CHARACTERIZATION OF THE 1122-TRANSLOCATION BREAKPOINT IN A MALIGNANT RHABDOID TUMOR

Malignant rhabdoid tumors are extremely aggressive soft-tissue sarcoma s that tend to be widely metastatic at diagnosis. These tumors were fi rst described as variants of the kidney neoplasm Wilms' tumor, althoug h tumors of similar clinicopathologic features have been cited in a va riety of extrarenal sites. Here, we have characterized the chromosomal translocation t(11;22)(p15.5;q11.23) from a retroperitoneal rhabdoid tumor. Somatic cell hybrids with segregated copies of the derivative 1 1 and derivative 22 chromosomes allowed sublocalization of the chromos ome 11 breakpoint to a 1- to 2-Mb region between the proximal marker D 11S12 and the distal locus tyrosine hydroxylase (TH). Translocation-as sociated aberrant fragments were identified by pulsed-field gel electr ophoresis, with the smallest resulting from BssHII digestion as detect ed with a probe for TH. These data indicate that the locus or loci dis rupted by this genetic abnormality might lie less than 60 kb proximal to this marker and place it in the chromosomal vicinity of genes invol ved in the etiologies of rhabdomyosarcoma, Wilms' tumor, and the conge nital overgrowth disorder, Beckwith-Wiedemann syndrome. Analysis of tw o other tumor-associated loci, EWS1 and NF2, that have been mapped to the general region of 22q11.2 indicated that they were not involved in this translocation breakpoint. Isolation of the genes present at this translocation junction on both chromosomes 11 and 22 may yield import ant clinicopathologic and genetic markers for this enigmatic tumor as well as other pediatric diseases. (C) 1994 Academic Press, Inc.