Isochromosomes are abnormal chromosomes that contain a duplication of a single chromosome arm (31). Isochromosome 17q [i(17q)] is the most common isochromosome associated with human neoplasia, including neuroectodermal tumors and medullablastomas, representing approx 3% of single or additional chromosomal abnormalities in carcinomas and hematologic malignancies, and occur in approx 21% of such cases during chronic myeloid leukemia disease progression (22). The i(17q) breakpoints cluster within 17p11.2, either in the very pericentromeric section or within the approx 4-Mb Smith-Magenis Syndrome common deletion region. An approx 240-kb interval (RNU3) encompassing the i(17q) breakpoint cluster region contains two LCRs, REPA and REPB, whereby two inverted copies of REPA (REPA1 and REPA2, approx 38 kb) separated by a single copy of REPB (REPB3, approx 48 kb), are followed by two inverted copies of REPB (REPB2, approx 43 kb, and REPB1, approx 49 kb). This arrangement provides the structural basis for the formation of large cruciform structures.
The i(17q) is consistent with a recombination mechanism between sister-chromatids mediated by a REPB1-REPB2 cruciform, which predicts formation of the dicentric i(17q) and an acentric chromosome that is expected to be lost (22). The i(17q) RNU3 LCRs are part of a complex array of LCRs involved in deletions and duplications leading to the Smith-Magenis Syndrome (31), the dup(17)(p11.2p11.2) syndrome (34), hereditary neuropathy with liability to pressure palsies (HNPP), and the Charcot-Marie-Tooth type 1 disease (CMT1A) (35,36) (Table 1). Also in these cases, the presence of strand exchange hotspots (37) strongly favors the concept of the formation of non-B DNA conformations as the molecular trigger for the rearrangements.
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