Microsatellite instability in sacral chordoma

Background and Objectives: Microsatellite instability (MIN) is an indirect marker of globally defective DNA mismatch repair in the neoplastic cells of cancer patients. Chordomas are rare, primary skeletal malignancies for whi ch few characteristic molecular genetic markers have been identified. Is MI N demonstratable in chordoma? Methods: We evaluated sacral chordomas from 12 patients with sacral chordom as for the presence of MIN at 9 different genetic loci from chromosomes 1p, 5q, 7q, 9p, lip, 12p, 13q, 17p, and 18q. Cells were scraped from glass sli des so that tumor and control DNA could be isolated and then amplified by p olymerase chain reaction (PCR). Heterozygosity indices were greater than or equal to 0.70. Results: Six patients (50%) demonstrated MIN for at least 1 locus, and 2 pa tients demonstrated loss of heterozygosity (LOH) for at least 1 locus. Only I individual's chordoma manifested microsatellite instability (MIN) and lo ss of heterozygosity (LOH). Another patient manifested no MIN but LOH at 9p and 18q. Interestingly, this individual had the most aggressive clinical c ancer course, presenting with lymph node metastasis and succumbing to wides pread metastatic disease. Conclusions: Chordomas can be added to the list of malignancies demonstrati ng MIN. LOH may prove to portend a worse prognosis than MIN when more tumor s are examined. (C) 2000 Wiley-Liss, Inc.