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 ShimizuKimmel 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 USARoberta BichiKimmel 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 USASimona ZupoKimmel 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 USAEvan NochKimmel 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 USAHansjuerg AldlerKimmel 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 USASashi 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 RaiKimmel 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 USALaura 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 NegriniLong Island Jewish Medical 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. CroceKimmel 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 USA
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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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