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 several hematologic conditions and particularly in the myeloproliferative disorders and myelodysplastic syndromes. The spectrum of diseases associated with 20q deletions suggests that such deletions may mark the site of a tumor suppressor gene that contributes to the regulation of normal multipotent hematopoietic progenitors. We present here the first detailed molecular analysis of 20q deletions associated with myeloid disorders. Thirty-four microsatellite primer pairs corresponding to loci on 20q have been used to study DNA samples from two cell lines and from highly purified peripheral blood granulocytes obtained from seven patients. In addition, Southern analysis of cell line DNA has been performed using 19 DNA probes that map to 20q. Three conclusions can be drawn from our results. Firstly, molecular heterogeneity of both centromeric and telomeric breakpoints was demonstrated, thus supporting the existence of a tumor suppressor gene on 20q. In addition many of the breakpoints have been mapped to small genetic intervals. Secondly, our results 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 physical maps and have refined the map positions of multiple genes. These results will facilitate attempts to identify candidate hematopoietic tumor suppressor genes on 20q.
Asimakopoulos
F A
FA
Department of Haematology, University of Cambridge, MRC Centre, UK.
White
N J
NJ
Nacheva
E
E
Green
A R
AR
D000782:Aneuploidy; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002890:Chromosomes, Human, Pair 20; D016147:Genes, Tumor Suppressor; D006801:Humans; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D009196:Myeloproliferative Disorders / Q000235:genetics*; D011110:Polymorphism, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D014407:Tumor Cells, Cultured