Molecular characterization of a myelodysplasia‐associated chromosome 7 inversion

Abstract

Summary. Chromosome 7 abnormalities are observed in a wide range of myeloid disorders, particularly myelodysplasia (MDS) and acute myeloid leukaemia (AML). Monosomy 7 and 7q deletions are the most frequent abnormalities, although translocations and inversions involving 7q also occur. The region 7q22±q34 may contain as many as four distinct minimal regions of deletion (MDRs), which are thought to contain one or more myeloid tumour-suppressor genes. We have defined previously the proximal breakpoint of a constitutional 7q22±q34 inversion, carried in a cell line derived from a member of a family with a history of MDS. A YAC clone spanning this breakpoint was identified. Both inversion breakpoints have now been cloned and sequenced, placing the proximal breakpoint 40 kb centromeric to the TAC2 (tachykinin 2) gene and the distal breakpoint 42 kb telomeric to the SSBP (mitochondrial single-stranded DNA-binding protein) gene. Sequence alignments revealed small (3±4 bp) duplications at the inversion breakpoints, suggesting that the mechanism of inversion involved the creation of staggered breaks and filling in of the overhanging ends. A 190-bp Alu±Alu deletion close to the distal breakpoint was also detected and may have contributed to the inversion.

Molecular Characterization of the Pericentric Inversion That Causes Differences Between Chimpanzee Chromosome 19 and Human Chromosome 17

“…Therefore, it is unlikely that filling of overhanging ends, rearrangement, and religation underlie the inversion. These mechanisms have been proposed to be involved in a number of leukemia-associated inversions and translocations of human chromosomes (Zhang et al 1995;Super et al 1997;Romana et al 1999;Todd et al 2001). Our findings imply that the molecular basis of the evolutionary inversion of chimpanzee 19 was nonhomologous recombination, which was not associated with complex additional rearrangements, such as deletions or duplications at the breakpoint regions.…”

The enigma of monosomy 7

“…Researchers tried to detail CDRs using then-current techniques such as restriction fragment-length polymorphism assessments, fluorescence in situ hybridization, and microsatellite surveys. Results from multiple laboratories were published around 1990, but the CDRs identified by each laboratory did not overlap (reviewed in Honda et al 36 and Todd et al 37 ) with the result that instead of narrowing down the location of the relevant CDRs, they were reported to be spread over the whole 7q region. Of note, at least these results showed that the conclusion that 7q22 and 7q34-36 bands were promising CDRs based on chromosomal analysis was incorrect.…”

Identification of a common microdeletion cluster in 7q21.3 subband among patients with myeloid leukemia and myelodysplastic syndrome

“…Detailed maps of regions deleted from individual patients were then generated from the results of loss of heterogeneity assays or fluorescence in situ hybridization. Unfortunately, the cumulative results from thousands of patients were confounded by the fact that the boundaries of commonly deleted regions derived by separate research groups showed a poor degree of overlap [3].…”