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 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.
Hofmann
W K
WK
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
Takeuchi
S
S
Xie
D
D
Miller
C W
CW
Hoelzer
D
D
Koeffler
H P
HP
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