title: Frequent loss of heterozygosity in the region of D1S450 at 1p36.2 in myelodysplastic syndromes.
abstract: To understand the underlying mechanisms in myelodysplastic syndromes (MDS) by identifying target tumor suppressor genes, we performed a detailed deletional 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 amplification of a total of 23 highly informative microsatellite sequences. We identified the commonly deleted region between D1S508 and D1S244. LOH of this region was found in five patients (13%). In addition, LOH at 1p was associated 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 identify somatic mutations in MDS. Our findings are consistent with the possible existence of an as-yet unknown tumor suppressor gene in this region that is altered in MDS.
authors.affiliation: Division of Hematology/Oncology, Cedars-Sinai Research Institute, UCLA School of Medicine, 8700 Beverly Boulevard, Suite B213, Los Angeles, CA 90048, USA. w.k.hofmann@em.uni-frankfurt.de
authors.forename: W K
authors.initials: WK
authors.lastname: Hofmann
authors.forename: S
authors.initials: S
authors.lastname: Takeuchi
authors.forename: D
authors.initials: D
authors.lastname: Xie
authors.forename: C W
authors.initials: CW
authors.lastname: Miller
authors.forename: D
authors.initials: D
authors.lastname: Hoelzer
authors.forename: H P
authors.initials: HP
authors.lastname: Koeffler
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000753:Anemia, Refractory / Q000235:genetics; D000754:Anemia, Refractory, with Excess of Blasts / Q000235:genetics; D001854:Bone Marrow Cells / Q000473:pathology; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D005260:Female; D006801:Humans; D015477:Leukemia, Myelomonocytic, Chronic / Q000235:genetics; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000473:pathology