Monoclonal Origin of Multicentric Kaposi's Sarcoma Lesions
Charles S. Rabkin, M.D., Siegfried Janz, M.D., Alex Lash, M.D., Allen E. Coleman, Elizabeth Musaba, M.D., Lance Liotta, M.D., Ph.D., Robert J. Biggar, M.D., and Zhengping Zhuang, M.D., Ph.D.
Background Kaposi's sarcoma has features of both hyperplasticproliferation and neoplastic growth. Multiple lesions, in whichspindle cells are prominent, often arise synchronously overwidely dispersed areas. We tested the hypothesis that the spindlecells in these multicentric lesions originate from a singleclone of precursor cells.
Methods To determine whether Kaposi's sarcoma is a monoclonaldisorder, we assessed the methylation patterns of the androgen-receptorgene (HUMARA) in multiple lesions from women with the acquiredimmunodeficiency syndrome. In polyclonal tissues, about halfthe copies of each HUMARA allele are methylated, whereas incells derived from a single clone all the copies of only oneallele are methylated. To minimize contamination by normal DNA,we used microdissection to isolate areas composed primarilyof spindle cells, the putative tumor cells.
Results Eight patients with a total of 32 tumors were studied.Of these tumors, 28 had highly unbalanced methylation patterns(i.e., predominant methylation of one HUMARA allele). In allthe tumors that had unbalanced methylation from a given patient,the same allele predominated.
Conclusions These data indicate that Kaposi's sarcoma is a disseminatedmonoclonal cancer and that the changes that permit the clonaloutgrowth of spindle cells occur before the disease spreads.
Source Information
From the Viral Epidemiology Branch (C.S.R., R.J.B.), the Laboratory of Genetics (S.J., A.E.C.), and the Laboratory of Pathology (A.L., L.L., Z.Z.), National Cancer Institute, Bethesda, Md.; and the University Teaching Hospital, Lusaka, Zambia (E.M.).
Address reprint requests to Dr. Rabkin at the Viral Epidemiology Branch, National Cancer Institute, EPN/434, Bethesda, MD 20892.
Clonality in Kaposi's Sarcoma
Gill P., Tsai Y., Rao A. P., Jones P., Diaz-Cano S. J., Wolfe H. J., Rabkin C. S., Janz S., Zhuang Z.
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N Engl J Med 1997;
337:570-572, Aug 21, 1997.
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