Chromosome 20 deletions in myeloid malignancies: reduction of the common deleted region, generation of a PAC/BAC contig and identification of candidate genes

Deletion of the long arm of chromosome 20 represents the most common chromo somal abnormality associated with the myeloproliferative disorders (MPDs) a nd is also found in other myeloid malignancies including myelodysplastic sy ndromes (MDS) and acute myeloid leukaemia (AML). Previous studies have iden tified a common deleted region (CDR) spanning approximately 8 Mb. We have n ow used G-banding, FISH or microsatellite PCR to analyse 113 patients with a 20q deletion associated with a myeloid malignancy. Our results define a n ew MPD CDR of 2.7 Mb, an MDS/AML CDR of 2.6 Mb and a combined 'myeloid' CDR of 1.7 Mb, We have also constructed the most detailed physical map of this region to date - a bacterial clone map spanning 5 Mb of the chromosome whi ch contains 456 bacterial clones and 202 DNA markers. Fifty-one expressed s equences were localized within this contig of which 37 lie within the MPD C DR and 20 within the MDS/AML CDR, Of the 16 expressed sequences (sis genes and 10 unique ESTs) within the 'myeloid' CDR, five were expressed in both n ormal bone marrow and purified CD34 positive cells. These data identify a s et of genes which are both positional and expression candidates for the tar get gene(s) on 20q.