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Previous Volume 353:1793-1801 October 27, 2005 Number 17 Next

	Full Text PDF PDA Full Text Supplementary Material Perspective by Chen, C.-Z. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear Related Article

ABSTRACT

Background MicroRNA expression profiles can be used to distinguish normal B cells from malignant B cells in patients with chronic lymphocytic leukemia (CLL). We investigated whether microRNA profiles are associated with known prognostic factors in CLL.

Methods We evaluated the microRNA expression profiles of 94 samples of CLL cells for which the level of expression of 70-kD zeta-associated protein (ZAP-70), the mutational status of the rearranged immunoglobulin heavy-chain variable-region (IgV_H) gene, and the time from diagnosis to initial treatment were known. We also investigated the genomic sequence of 42 microRNA genes to identify abnormalities.

Results A unique microRNA expression signature composed of 13 genes (of 190 analyzed) differentiated cases of CLL with low levels of ZAP-70 expression from those with high levels and cases with unmutated IgV_H from those with mutated IgV_H. The same microRNA signature was also associated with the presence or absence of disease progression. We also identified a germ-line mutation in the miR-16-1–miR-15a primary precursor, which caused low levels of microRNA expression in vitro and in vivo and was associated with deletion of the normal allele. Germ-line or somatic mutations were found in 5 of 42 sequenced microRNAs in 11 of 75 patients with CLL, but no such mutations were found in 160 subjects without cancer (P<0.001).

Conclusions A unique microRNA signature is associated with prognostic factors and disease progression in CLL. Mutations in microRNA transcripts are common and may have functional importance.

Source Information

From the Department of Molecular Virology, Immunology, and Medical Genetics and Comprehensive Cancer Center, Ohio State University, Columbus (G.A.C., A.C., G.D.L., M.S., S.E.W., M.V.I., R.V., N.I.S., M.F., R.I., T.P., F.P., C.R., H.A., S.V., C.L., C.M.C.); the Department of Experimental and Diagnostic Medicine, Interdepartment Center for Cancer Research, University of Ferrara, Ferrara, Italy (M.F., M.N.); the Kimmel Cancer Center, Thomas Jefferson University, Philadelphia (R.G., C.S.); and the Department of Medicine, University of California, San Diego, La Jolla (L.R., T.J.K.).

Address reprint requests to Dr. Croce at Ohio State University, Comprehensive Cancer Center, Wiseman Hall, Rm. 385K, 400 12th Ave., Columbus, OH 43210, or at carlo.croce{at}osumc.edu.

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