Absence of microsatellite instability in primary myelodysplastic syndrome

Using polymerase chain reaction (PCR), we examined a panel of 10 microsatel lite markers (BAT26, BAT40, D2S123, D4S171, D8S87, D10S197, D12S89, Tp53, D 18S58, PLCpr) covering nine chromosomal arms for microsatellite instability (MSI) in 29 patients with primary MDS. Bone marrow DNA was compared with c orresponding constitutional DNA derived fr om buccal epithelial cells. Apar t from BAT26 and BAT40 that were mononucleotide (poly A) repeats, the other s were dinucleotide (CA) repeats. The patients comprised 10 cases of refrac tory anemia. (RA), three cases of refractory anemia with ringed sideroblast s (RARS), nine cases of refractory anemia with excess of blasts (RAEB), fou r cases of refractory anemia with excess of blasts in transformation (RAEBt ), and three cases of chronic myelomonocytic leukemia (CMML). Serial sample s were available in seven patients, in which four showed transformation int o higher disease grade or acute myeloid leukemia (AML). Genetic alterations at one locus (three at D2S123, one at D4S171) were evident in four cases, and loss of heterozygosity at Tp53 was detected in one case. Accordingly, n one of the 29 patients with primary MDS nor the seven with disease progress ion in this study exhibited MSI. This shows that MSI may not be important i n the pathogenesis or progression of MDS in contrast to other genetic mecha nisms, notably recurrent chromosomal abnormalities that dysregulate the exp ression or function of genes controlling cell growth, differentiation and a poptosis.