Characterisation of dicentric 17;20 chromosomes in MDS and AML: Evidence for the retention of critical genes accompanying chromosome deletion
We have compared a series of unbalanced translocations between chromosomes 17 and 20, to investigate the significance of the dicentric chromosome abnormality, dic(17;20). The dic(17;20) of acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS) combines the recurrent deletions of 17p and 20q, which are well-known abnormalities in these diseases.
We have identified eleven cases of MDS or AML with unbalanced translocations between chromosomes 17 and 20, with net deletion of 17p and 20q material. These were identified by chromosome painting of cases with cryptic chromosome 17 and 20 abnormalities. Chromosomes were compared using G-banding, multicolour banding (mBAND) and fluorescence in situ hybridisation (FISH) with locus-specific and centromere probes.
All of the 17;20 translocations apparently produced a dicentric chromosome. As dicentric chromosomes are unusual, this may point to important features of chromosome 17 and 20 deletions.
Unstable dicentrics had often undergone complex rearrangements but were never lost. These rearrangements appeared to increase stability while preserving some 17p and 20q material. The dicentric chromosome breakpoints varied, so there was no suggestion that a critical abnormal fusion gene was formed.
The D20S108 locus from the common deleted region at 20q12 was deleted in all cases but TP53 was not always lost, suggesting a more distal target for 17p deletions in myeloid malignancy.
We hypothesise that there are sequences on proximal 17p and proximal 20q that must be retained during 17p and 20q deletions of AML and MDS. This would explain the apparent necessity for a dicentric chromosome to be formed, and the apparently contradictory loss of a centromere from some of the dicentrics.