Frequent deletions and down-regulation of micro- RNA genes <i>miR15</i> and <i>miR16</i> at 13q14 in chronic lymphocytic leukemia
George A. CalinKimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107 USA; Clinical Immunology, National Institute for Research on Cancer, 16132 Genoa, Italy Europe; Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030 USA; Long Island Jewish Medical Center, New Hyde Park, NY 11040 USA; and Department of Medicine, University of California at San Diego, La Jolla, CA 92093 USACalin Dan DumitruKimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107 USA; Clinical Immunology, National Institute for Research on Cancer, 16132 Genoa, Italy Europe; Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030 USA; Long Island Jewish Medical Center, New Hyde Park, NY 11040 USA; and Department of Medicine, University of California at San Diego, La Jolla, CA 92093 USAMasayoshi ShimizuSidney Kimmel Cancer CenterRoberta BichiLong Island Jewish Medical CenterSimona ZupoLong Island Jewish Medical CenterEvan NochSidney Kimmel Cancer CenterHansjuerg AldlerLong Island Jewish Medical CenterSashi RattanKimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107 USA; Clinical Immunology, National Institute for Research on Cancer, 16132 Genoa, Italy Europe; Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030 USA; Long Island Jewish Medical Center, New Hyde Park, NY 11040 USA; and Department of Medicine, University of California at San Diego, La Jolla, CA 92093 USAMichael J. KeatingKimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107 USA; Clinical Immunology, National Institute for Research on Cancer, 16132 Genoa, Italy Europe; Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030 USA; Long Island Jewish Medical Center, New Hyde Park, NY 11040 USA; and Department of Medicine, University of California at San Diego, La Jolla, CA 92093 USAKanti RaiSidney Kimmel Cancer CenterLaura Z. RassentiKimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107 USA; Clinical Immunology, National Institute for Research on Cancer, 16132 Genoa, Italy Europe; Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030 USA; Long Island Jewish Medical Center, New Hyde Park, NY 11040 USA; and Department of Medicine, University of California at San Diego, La Jolla, CA 92093 USAThomas J. KippsKimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107 USA; Clinical Immunology, National Institute for Research on Cancer, 16132 Genoa, Italy Europe; Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030 USA; Long Island Jewish Medical Center, New Hyde Park, NY 11040 USA; and Department of Medicine, University of California at San Diego, La Jolla, CA 92093 USAMassimo NegriniSidney Kimmel Cancer CenterFlorencia BullrichKimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107 USA; Clinical Immunology, National Institute for Research on Cancer, 16132 Genoa, Italy Europe; Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030 USA; Long Island Jewish Medical Center, New Hyde Park, NY 11040 USA; and Department of Medicine, University of California at San Diego, La Jolla, CA 92093 USACarlo M. CroceLong Island Jewish Medical Center
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Micro-RNAs (miR genes) are a large family of highly conserved noncoding genes thought to be involved in temporal and tissue-specific gene regulation. MiRs are transcribed as short hairpin precursors ( approximately 70 nt) and are processed into active 21- to 22-nt RNAs by Dicer, a ribonuclease that recognizes target mRNAs via base-pairing interactions. Here we show that miR15 and miR16 are located at chromosome 13q14, a region deleted in more than half of B cell chronic lymphocytic leukemias (B-CLL). Detailed deletion and expression analysis shows that miR15 and miR16 are located within a 30-kb region of loss in CLL, and that both genes are deleted or down-regulated in the majority ( approximately 68%) of CLL cases.
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