"This discovery is quite surprising," said Charles S. Rabkin, M.D., who led the study in the National Cancer Institute's (NCI) Viral Epidemiology Branch. "Kaposi's sarcoma behaves so differently from other tumors that it has not been clear whether it derives from one cell or many, or even whether it should be considered a true cancer."
This study, which NCI conducted in collaboration with University Teaching Hospital, Lusaka, Zambia, strongly suggests that Kaposi's sarcoma is monoclonal. That is, like other cancers, it has its origin in a single, genetically altered cell which multiplies and spreads.
Most cancers begin with a primary tumor that can later metastasize to other parts of the body. In Kaposi's sarcoma, however, there is no sign of a primary tumor. Instead, the characteristic lesions -- purplish patches, raised plaques, and nodules -- appear at about the same time in widely separated areas of the body.
Scientists had hypothesized that these lesions arise independently from different cells. To test this idea, Rabkin and his colleagues analyzed the tumor cells from multiple lesions taken from eight women with Kaposi's sarcoma.
The researchers analyzed Kaposi's sarcoma in women because of a special characteristic of the two X chromosomes that women inherit (unlike men who have one X and one Y chromosome). In each of a woman's cells, one X chromosome has undergone methylation, a chemical change that can inactivate genes. The other X chromosome is unmethylated. Normally, which X chromosome is methylated varies from cell-to-cell. But in cancer tissue, the methylation patterns of the two X chromosomes are quite regular -- the same X chromosome is methylated in every cell.
In this study, methylation patterns were similar in all tumors from any given patient, indicating that the tumor cells were all related. The finding suggests that the abnormal cells in Kaposi's sarcoma arise at a single site, then circulate through the body to spots on skin and organs where they proliferate. While their technique could only be used to analyze tumors from women, the researchers believe the finding applies equally to men and women with Kaposi's sarcoma.
"Our data indicate that the genetic changes that lead to Kaposi's sarcoma occur before the disease spreads, as in other cancers," said Rabkin. "That means we can expect to learn more about the disease now by looking for the kinds of genetic changes, such as mutations and rearrangements, that are often implicated in cancer."
Kaposi's sarcoma is the most common tumor in AIDS patients. It also occurs in others with suppressed immune function, such as transplant patients who take immunosuppressive drugs. The incidence has grown very rapidly in the past 15 years with increasing rates of HIV infection and AIDS. It is estimated that about 8,000-12,000 new cases are diagnosed in the U.S. each year.
* The study is titled, "Monoclonal Origin of Multicentric Kaposi's Sarcoma Lesions." The authors are Rabkin CS, Janz A, Lash A, Coleman AE, Musaba E, Liotta L, Biggar R, and Zhuang Z. New England Journal of Medicine 336, April 2, 1997.
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