Monoclonal origin of multicentric Kaposi's sarcoma lesions.
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.
Rabkin
C S
CS
Viral Epidemiology Branch, National Cancer Institute, Bethesda, MD 20892, USA.
Janz
S
S
Lash
A
A
Coleman
A E
AE
Musaba
E
E
Liotta
L
L
Biggar
R J
RJ
Zhuang
Z
Z
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications; D000328:Adult; D000483:Alleles; D002999:Clone Cells; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006801:Humans; D016133:Polymerase Chain Reaction; D011944:Receptors, Androgen / Q000235:genetics*; D012514:Sarcoma, Kaposi / Q000209:etiology / Q000235:genetics* / Q000473:pathology
D004273:DNA, Neoplasm; D011944:Receptors, Androgen