MOLECULAR ANALYSIS OF CHROMOSOME 20Q DELETIONS ASSOCIATED WITH MYELOPROLIFERATIVE DISORDERS AND MYELODYSPLASTIC SYNDROMES

Acquired deletions of the long arm of chromosome 20 are found in sever al hematologic conditions and particularly in the myeloproliferative d isorders and myelodysplastic syndromes. The spectrum of diseases assoc iated with 20q deletions suggests that such deletions may mark the sit e of a tumor suppressor gene that contributes to the regulation of nor mal multipotent hematopoietic progenitors. We present here the first d etailed molecular analysis of 20q deletions associated with myeloid di sorders. Thirty-four microsatellite primer pairs corresponding to loci on 20q have been used to study DNA samples from two cell lines and fr om highly purified peripheral blood granulocytes obtained from seven p atients. In addition, Southern analysis of cell line DNA has been perf ormed using 19 DNA probes that map to 20q. Three conclusions can be dr awn from our results. Firstly, molecular heterogeneity of both centrom eric and telomeric breakpoints was demonstrated, thus supporting the e xistence of a tumor suppressor gene on 20q. In addition many of the br eakpoints have been mapped to small genetic intervals. Secondly, our r esults define a commonly deleted region of 16-21 cM which contains ADA , PLC1 TOP1 SEMG1, and PPGB. Several candidate tumor suppressor genes lie outside the common deleted region including SRC, HCK, p107, PTPN1, and CEBP beta. Thirdly, the data allow integration of genetic and phy sical maps and have refined the map positions of multiple genes, These results will facilitate attempts to identify candidate hematopoietic tumor suppressor genes on 20q. (C) 1994 by The American Society of Hem atology.