MONOCLONAL ORIGIN OF MULTICENTRIC KAPOSIS-SARCOMA LESIONS

Background Kaposi's sarcoma has features of both hyperplastic prolifer ation and neoplastic growth. Multiple lesions, in which spindle cells are prominent, often arise synchronously over widely dispersed areas. We tested the hypothesis that the spindle cells in these multicentric lesions originate from a single clone of precursor cells. Methods To d etermine whether Kaposi's sarcoma is a monoclonal disorder, we assesse d the methylation patterns of the androgen-receptor gene (HUMARA) in m ultiple lesions from women with the acquired immunodeficiency syndrome . In polyclonal tissues, about half the copies of each HUMARA allele a re methylated, whereas in cells derived from a single clone all the co pies of only one allele are methylated. To minimize contamination by n ormal DNA, we used microdissection to isolate areas composed primarily of spindle cells, the putative tumor cells.Results Eight patients wit h a total of 32 tumors were studied. Of these tumors, 28 had highly un balanced methylation patterns (i.e., predominant methylation of one HU MARA allele). In all the tumors that had unbalanced methylation from a given patient, the same allele predominated. Conclusions These data i ndicate that Kaposi's sarcoma is a disseminated monoclonal cancer and that the changes that permit the clonal outgrowth of spindle cells occ ur before the disease spreads. (C) 1997, Massachusetts Medical Society .