A novel member of the WD-repeat gene family, WDR11, maps to the 10q26 region and is disrupted by a chromosome translocation in human glioblastoma cells

Allelic deletions of 10q25-26 and 19q13.3-13.4 are the most common genetic alterations in glial tumors. We have identified a balanced t(10;19) recipro cal translocation in the A172 glioblastoma cell line which involves both cr itical regions on chromosomes 10 and 19. In addition, loss of an entire cop y of chromosome 10 has occurred in this cell line suggesting that the trans location event may provide a highly specific critical inactivating event in a gene responsible for tumorigenesis. Positional cloning of this transloca tion breakpoint resulted in the identification of a novel chromosome 10 gen e, WDR11, which is a member of the WD-repeat gene family. The WDR11 gene is ubiquitously expressed, including normal brain and glial tumors. WDR11 is composed of 29 exons distributed over 58 kilobases and oriented towards the telomere. The translocation resulted in deletion of exon 5 and consequentl y fusion of intron 4 of WDR11 to the 3' untranslated region of a novel memb er, ZNF320, of the Kruppel-like zinc finger gene family. Since ZNF320 is or iented toward the centromere of chromosome 19, both genes appeared on the s ame derivative chromosome der(10). The chimeric transcript encodes the WDR1 1 polypeptide, which is truncated after the second of six WD-repeats. ZNF32 0 is also expressed in A172 cells, although it is not clear if the transloc ation affects the expression of the altered gene because of the presence of another unrearranged gene on chromosome 19. We suggest that, because of it s localization in a region frequently showing LOH and the observation of in activation of this gene in glioblastoma cells, WDR11 is a candidate gene fo r the frequently proposed tumor suppressor gene in 10q25-26 which is involv ed in tumorigenesis of glial and other tumors showing frequent alterations in the distal 10q region.