MOLECULAR HETEROGENEITY AT THE BREAKPOINTS OF SMALLER 20Q DELETIONS

Deletions of the long arm of chromosome 20 [del(20q)] are recurring ab normalities in patients with myeloid disorders. Although variable in s ize, these deletions are usually interstitial. With the object of defi ning a commonly deleted region for smaller 20q deletions, we used quan titative Southern blot analysis complemented by restriction fragment l ength polymorphism (RFLP) analysis to determine the copy number at 15 loci spanning 20q. The proximal breakpoints of three such deletions we re found to separate HCK and the growth hormone releasing factor (GHRF ) locus near the centromeric boundary of band 20q11.2. The distal brea kpoints were localized to the vicinity of the D20S22 locus in band q13 .1. A candidate tumor suppressor gene, RBL2, and the SRC oncogene were both located within the commonly deleted region. Six loci in terminal region q 13.2-q13.3 were conserved on these del(20q) chromosomes, the reby confirming that the deletions were interstitial. Molecular hetero geneity at one and possibly both deletion breakpoints rules out the pa thological involvement of loci at these sites. Instead, loss of a tumo r suppressor locus from within the commonly deleted region may contrib ute to deregulated hemopoiesis. (C) 1994 Wiley-Liss, Inc.