Microsatellite instability is infrequent in sporadic adult gliomas

Microsatellite instability (MSI) is a form of genomic instability in tumors that may reflect mechanisms underlying carcinogenesis. Assessment of MSI i n various types of sporadic tumors is therefore relevant to an understandin g of molecular pathogenesis. In the case of sporadic adult gliomas, destabi lization of mononucleotide, dinucleotide, and longer repeat sequences has b een reported in high-grade tumors, though published estimates of the freque ncy of MSI vary widely. In the present work, we quantitated the frequency o f length alterations at three microsatellite loci in 26 glioma/normal tissu e pairs and at nine additional loci in 16 of the pairs. We analyzed di- and tetranucleotide markers, including five previously reported to be unstable in gliomas, and examined mostly high-grade tumors, both diploid and aneupl oid. A large proportion of the tumor and normal brain specimens had no dete ctable activity of the DNA repair protein O-6-methylguanine-DNA methyltrans ferase, a prevalent phenotypic trait in these tissues that we thought might be associated with MSI. We observed no length alterations in 222 sequence analyses, and estimate the frequency of MSI in our tumor sample as <0.45% u nstable sequences among all sequences examined, or <3.9% gliomas with unsta ble sequences. We conclude that microsatellite length alterations are infre quent in our tumor population, and interpret currently available literature to indicate that the frequency of MSI is low in sporadic adult gliomas.