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 Blood, 4 June 2009, Vol. 113, No. 23, pp. 5938-5941.
Prepublished online as a Blood First Edition Paper on February 27, 2009; DOI 10.1182/blood-2008-09-179168.

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LYMPHOID NEOPLASIA

Brief report

Tumor suppressor microRNAs are underrepresented in primary effusion lymphoma and Kaposi sarcoma

Andrea J. O'Hara1, Ling Wang1, Bruce J. Dezube2, William J. Harrington, Jr3, Blossom Damania1, and Dirk P. Dittmer1

1 Department of Microbiology and Immunology, Lineberger Comprehensive Cancer Center, Center for AIDS Research at the University of North Carolina at Chapel Hill; 2 Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA; and 3 Viral Oncology Program, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, FL

The presence of tumor-specific microRNAs reflects tissue of origin and tumor stage. We show that the absence of miRNAs likewise can be used to determine tumor origin (miR-155) and proliferation state because tumor suppressor miRNAs (miR-222/221, let-7 family) were significantly down-regulated in primary effusion lymphoma (PEL) and in Kaposi sarcoma (KS), an endothelial cell tumor. PEL and KS are associated with KS-associated herpesvirus infection. We identified 15 virally regulated miRNAs in latently infected, nontumorigenic endothelial cells. MiR-143/145 were elevated only in KS tumors, not virally infected endothelial cells. Thus, they represent tumor-specific, rather than virus-specific, miRNAs. Because many tumor suppressor proteins are wild-type in KS and PEL, down-regulation of multiple tumor suppressor miRNAs provides a novel, alternative mechanism of transformation.


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