Molecular cytogenetics localizes two new breakpoints on 11q23.3 and 21q11.2 in myelodysplastic syndrome with t(11;21) translocation

Translocation t(11;21)(q24;q11.2) is a rare but recurrent chromosomal abnor mality associated with myelodysplastic syndrome (MDS) that until now has no t been characterized at the molecular level. We report here results of a mo lecular cytogenetic analysis of this translocation in a patient with refrac tory anemia. Using FISH with a panel of 11q and 21q cosmid/YAC probes, we l ocalized the chromosome I I breakpoint at q23.3 in a region flanked by CP-9 21G9 and CP-939H3 YACs, distal to the HRX/MLL locus frequently involved in acute leukemias, The chromosome 21 breakpoint was mapped in a 800-kb fragme nt inserted into the CP-145E3 YAC at 21q11.2, proximal to the AML I gene. I t is noteworthy that in all four cases with a t(11;21) reported until now, a second der(11)t(11;21) and loss of normal chromosome 11 could be observed either at diagnosis or during the course of the disease. Since in our case heteromorphism was detected by FISH on the centromeric region of the two d er(11), the second der(11) chromosome could be the result of a mitotic reco mbination that had occurred on the long arm of chromosome 11, rather than o f duplication of the original der(11). Constancy of secondary karyotypic ch anges resulting in an extra copy of the putative chimeric gene at der(11), loss of 11qter sequences, and partial trisomy 21 suggest that neoplastic pr ogression of MDS cases with a t(11;21) may be driven by the same mechanism( s). Genes Chromosomes Cancer 24:199-206, 1999. (C) 1999 Wiley-Liss, Inc.