Frequent loss of heterozygosity in the region of D1S450 at 1p36.2 in myelodysplastic syndromes

To understand the underlying mechanisms in myelodysplastic syndromes (MDS) by identifying target tumor suppressor genes, we performed a detailed delet ional mapping of the short arm of chromosome 1 in 38 paired samples of bone marrow and peripheral blood obtained from individuals with MDS by PCR ampl ification of a total of 23 highly informative microsatellite sequences. We identified the commonly deleted region between D1S508 and D1S244. LOH of th is region was found in five patients (13%). In addition, LOH at 1p was asso ciated with a poor clinical outcome, suggesting that the deletion of a gene in this region may be involved in the course of this disease. By analyzing the chromosomal map of this region, we found TNFRSF12 as a candidate tumor suppressor gene. However, our search for mutations in this gene did not id entify somatic mutations in MDS. Our findings are consistent with the possi ble existence of an as-yet unknown tumor suppressor gene in this region tha t is altered in MDS. (C) 2001 Elsevier Science Ltd. All rights reserved.