Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia

  1. George Adrian Calin*,
  2. Calin Dan Dumitru*,
  3. Masayoshi Shimizu*,
  4. Roberta Bichi*,
  5. Simona Zupo,
  6. Evan Noch*,
  7. Hansjuerg Aldler*,
  8. Sashi Rattan*,
  9. Michael Keating,
  10. Kanti Rai§,
  11. Laura Rassenti,
  12. Thomas Kipps,
  13. Massimo Negrini*,
  14. Florencia Bullrich*, and
  15. Carlo M. Croce*,
  1. *Kimmel 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
  1. Contributed by Carlo M. Croce

Abstract

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 (≈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 (≈68%) of CLL cases.

Footnotes

  • To whom correspondence should be addressed at: Kimmel Cancer Center, Thomas Jefferson University, 233 South 10th Street, 1050 Bluemle Life Science Building, Philadelphia, PA 19107. E-mail: Carlo.Croce{at}mail.tju.edu.

  • Abbreviations:
    1. CLL, chronic lymphocytic leukemia

    2. LOH, loss of heterozygosity

    3. miRNA, micro-RNA

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