Isolation of genes from the rhabdoid tumor deletion region in chromosome band 22q11.2

We employed exon trapping and large-scale genomic sequence analysis of two bacterial artificial chromosome clones to isolate genes from the region bet ween the IGLC and BCR in chromosome 22q11.2. At the time these studies were initiated, one previously identified gene, GNAZ, was known to map to this region, Two genes, RTDR1 and RAB36, were cloned from this portion of 22q11, which is heterozygously or homozygously deleted in pediatric rhabdoid tumo rs of the brain, kidney and soft tissues. RTDR1 is a novel gene with a slig ht homology to a yeast vacuolar protein. RAB36 is a member of the Rab famil y of proteins. A series of primary rhabdoid tumors with chromosome 22q11 de letions were screened for mutations in the coding sequences of RTDR1, GNAZ and RAB36, but did not demonstrate any disease-specific alterations. Recent ly, INII, which maps to the distal portion of the deletion region in 22q11, was identified as the candidate rhabdoid tumor suppressor gene. Further st udies of RTDR1 and RAB36 are required to determine whether their absence co ntributes to the progression of rhabdoid tumors. Alternatively, these genes may be candidates for other diseases that map to human chromosome 22. (C) 2000 Elsevier Science B.V. All rights reserved.