Molecular heterogeneity at the breakpoints of smaller 20q deletions

Abstract

Deletions of the long arm of chromosome 20 [del(20q)] are recurring abnormalities in patients with myeloid disorders. Although variable in size, these deletions are usually interstitial. With the object of defining a commonly deleted region for smaller 20q deletions, we used quantitative Southern blot analysis complemented by restriction fragment length polymorphism (RFLP) analysis to determine the copy number at 15 loci spanning 20q. The proximal breakpoints of three such deletions were found to separate HCK and the growth hormone releasing factor (GHRF) locus near the centromeric boundary of band 20q11.2. The distal breakpoints 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 q13.2-q13.3 were conserved on these del(20q) chromosomes, thereby confirming that the deletions were interstitial. Molecular heterogeneity at one and possibly both deletion breakpoints rules out the pathological involvement of loci at these sites. Instead, loss of a tumor suppressor locus from within the commonly deleted region may contribute to deregulated hemopoiesis.

Chromosome 20 deletions in myeloid malignancies: reduction of the common deleted region, generation of a PAC/BAC contig and identification of candidate genes

“…A second explanation is that breakpoints are clustered at speci®c sites which are hotspots for recombination. However, a number of investigators have reported that both centromeric and telomeric breakpoints of 20q deletions are very heterogeneous Bench et al, 1998a;Hollings, 1994;Roulston et al, 1993;Wang et al, 1998) arguing against this possibility. We therefore favour a third possibility, namely that more than one target gene exists on 20q.…”

“…FISH mapping by Le Beau and colleagues (Roulston et al, 1993) provided the ®rst molecular identi®cation of a common deleted region (CDR) between RPN2 and D20S17, a region of approximately 13 Mb. Molecular analysis using microsatellite PCR and Southern blotting re®ned the proximal boundary to D20S174 and demonstrated that both the centromeric and telomeric breakpoints were heterogeneous Hollings, 1994).…”

Characterization of chromosome arm 20q abnormalities in myeloid malignancies using genome‐wide single nucleotide polymorphism array analysis

“…Defining a minimal commonly deleted region (CDR) or commonly retained region (CRR) for a disease allows for the identification of tumor suppressor genes or oncogenes within the interval that may have a pathogenetic role or that may serve as a therapeutic target. The 20q CDR in myeloid malignancies has been investigated by FISH and microsatellite analysis (Roulston et al, 1993; Asimakopoulos et al, 1994; Hollings, 1994; Bench et al, 1998, 2000; Wang et al, 2000; MacGrogan et al, 2001; Douet‐Guilbert et al, 2008; Schaub et al, 2009), but due to the limited resolution of these techniques, precise delineation of the region has been difficult. Recently, single nucleotide polymorphism arrays (SNP‐A) have been applied for high‐resolution whole genome scanning in myeloid malignancies (Fitzgibbon et al, 2005; Griffiths et al, 2005; Gondek et al, 2007, 2008; Mohamedali et al, 2007; Dunbar et al, 2008; Gupta et al, 2008; Maciejewski et al, 2008; Szpurka et al, 2008; Jankowska et al, 2009).…”

Deletion of the long arm of chromosome 20 in a patient with chronic neutrophilic leukemia: Cytogenetic findings in chronic neutrophilic leukemia

“…In addition to our patients, we reviewed these cases (Table I). One case showed concom-commonly deleted regions of chromosome 20 [11,12].…”