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Monoclonal origin of multicentric Kaposi's sarcoma lesions. N Engl J Med 1997 Apr 03;336(14):988-93

Date

04/03/1997

Pubmed ID

9077377

DOI

10.1056/NEJM199704033361403

Abstract

BACKGROUND: Kaposi's sarcoma has features of both hyperplastic proliferation 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 determine whether Kaposi's sarcoma is a monoclonal disorder, we assessed the methylation patterns of the androgen-receptor gene (HUMARA) in multiple lesions from women with the acquired immunodeficiency syndrome. In polyclonal tissues, about half the copies of each HUMARA allele are methylated, whereas in cells derived from a single clone all the copies of only one allele are methylated. To minimize contamination by normal DNA, we used microdissection to isolate areas composed primarily of 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 all the tumors that had unbalanced methylation from a given patient, the same allele predominated.

CONCLUSIONS: These data indicate that Kaposi's sarcoma is a disseminated monoclonal cancer and that the changes that permit the clonal outgrowth of spindle cells occur before the disease spreads.

Author List

Rabkin CS, Janz S, Lash A, Coleman AE, Musaba E, Liotta L, Biggar RJ, Zhuang Z

Author

Siegfried Janz MD Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Acquired Immunodeficiency Syndrome
Adult
Alleles
Clone Cells
DNA Methylation
DNA, Neoplasm
Female
Heterozygote
Humans
Polymerase Chain Reaction
Receptors, Androgen
Sarcoma, Kaposi
jenkins-FCD Prod-410 e9586552fe7f53c71f7923aa6e27aeabbd3c2473