Allelic loss in the progression of myelodysplastic syndrome.
To elucidate the genetic events that may play an important role in the progression of myelodysplastic syndrome (MDS) to acute myeloid leukemia (AML), we performed allelotype analysis of 24 individuals using matched MDS and AML samples from the same patients. Because the evolution can take years to occur, we used DNAs extracted from archival samples. These samples were analyzed with 79 microsatellite markers, which mapped to each of the autosomal arms except the short arms of the acrocentric chromosomes. Loss of heterozygosity on at least one locus was observed in 18 of the 24 cases (75%) as the disease progressed. Frequent allelic loss in >20% of the informative cases was observed on chromosome arms 6q (31%), 7p (23%), 10p (31%), 11q (27%), 14q (25%), and 20q (23%). Although cytogenetic information was available for many of our cases with allelic loss on 6q, 7p, 10p, 11q, 14q, and 20q, no deletions were observed on these arms. Fractional allelic loss, calculated for each sample as the total number of chromosomal arms lost per total number of arms with information, showed a median value of 0.06 and a mean of 0.15 (range, 0-0.59). No microsatellite instability at more than one marker was found in any of the samples. These results suggest that tumor suppressor genes exist on 6q, 7p, 10p, 11q, 14q, and 20q that have an important role in the evolution of MDS to AML when they are mutated.
Mori
N
N
Department of Medicine, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, California 90048, USA.
Morosetti
R
R
Hoflehner
E
E
Lübbert
M
M
Mizoguchi
H
H
Koeffler
H P
HP
D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D000753:Anemia, Refractory / Q000235:genetics; D000754:Anemia, Refractory, with Excess of Blasts / Q000235:genetics; D001853:Bone Marrow / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D016147:Genes, Tumor Suppressor / Q000235:genetics; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics*; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics*