Breakpoint heterogeneity in (2;3)(p15-23;q26) translocations involving EVI1 in myeloid hemopathies.

Abstract Several chromosomal rearrangements involving band 3q26 are known to induce EVI1 overexpression. They include inv(3)(q21q26), t(3;3)(q21;q26), t(3;21)(q26;q22) and t(3;12)(q26;p13). Translocations involving the short arm of chromosome 2 and 3q26 have been reported in more than 50 patients with myeloid disorders. However, although the breakpoints on 2p are scattered over a long segment, their distribution had only been analyzed in 9 patients. We performed fluorescent in situ hybridization with a library of BAC (Bacterial Artificial Chromosome) clones in 4 patients with t(2;3)(p15–23;q26). Our results combined with those of the 9 previously reported patients showed scattering of the breakpoints in 2 regions. A 1.08 Mb region in band 2p21 encompassing the MTA3 , ZFP36L2 and THADA genes was documented in 5 patients. A second region of 1.83 Mb in band 2p16.1 was identified in 8 patients. Four patients showed clustering around the BCL11A gene and the remaining 4 around a long intergenic non-coding RNA, FLJ30838 . These regions are characterized by the presence of regulatory sequences (CpG islands and promoters) that could be instrumental in EVI1 overexpression.