SCREENING FOR LOSS OF HERTEROZYGOSITY AND MICROSATELLITE INSTABILITY IN OLIGODENDROGLIOMAS

To assess the frequency of loss of heterozygosity (LOH) and microsatel lite instability (MI) in oligodendrogliomas, we performed an extensive screening of 16 oligodendrogliomas and nine anaplastic oligodendrogli omas by using 132 microsatellite markers on chromosomes I through 12 a nd 15 through 21. In total, 3,135 loci were examined in 25 tumor sampl es. Only 33/1,965 (1.7%) of oligodendroglioma (low-grade) and 11/1,070 (1.0%) of anaplastic oligodendroglioma (high-grade) loci exhibited MI . High-frequency LOH regions were identified on chromosome arms 1p (31 -73% for oligodendrogliomas and 60-100% for anaplastic oligodendroglio mas) and 19q (23-69% for oligodendrogliomas and 100% for anaplastic ol igodendrogliomas). In addition, regions on chromosomes 4, 6, and 11 we re found to be lost in 30-80% of both oligodendrogliomas and anaplasti c oligodendrogliomas. Increased LOH frequency of chromosome 17 (38-40% ) was found only in high-grade oligodendrogliomas. The differences in LOH frequencies between low-grade and high-grade oligodendrogliomas in all loci combined and at three loci (DIS447, DIS226, and DIS252) on c hromosome arm 1p were determined to be statistically significant [chi( 2)(1) = 20.2, P < 0.0001, and Fisher's exact test respective P values: 0.01, 0.03, and 0.02]. Our results provide evidence that microsatelli te instability does not play an important role the development of olig odendrogliomas. Furthermore, high LOH frequency on chromosomes 6 and 1 1 in addition to that identified previously on chromosomes 1, 19, and 4 suggests that multiple candidate tumor suppressor genes on these chr omosomes may underlie the processes of initiation and/or progression i n oligodendroglioma tumorigenesis. (C) 1998 Wiley-Liss, Inc.