Better explicating the strengths and shortcomings of these models will help refine projections and improve transparency in the years ahead.
Image credit: Witsawat.S.
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Contributed by Carlo M. Croce, December 29, 2003
Abstract
A large number of tiny noncoding RNAs have been cloned and named microRNAs (miRs). Recently, we have reported that miR-15a and miR-16a, located at 13q14, are frequently deleted and/or down-regulated in patients with B cell chronic lymphocytic leukemia, a disorder characterized by increased survival. To further investigate the possible involvement of miRs in human cancers on a genome-wide basis, we have mapped 186 miRs and compared their location to the location of previous reported nonrandom genetic alterations. Here, we show that miR genes are frequently located at fragile sites, as well as in minimal regions of loss of heterozygosity, minimal regions of amplification (minimal amplicons), or common breakpoint regions. Overall, 98 of 186 (52.5%) of miR genes are in cancer-associated genomic regions or in fragile sites. Moreover, by Northern blotting, we have shown that several miRs located in deleted regions have low levels of expression in cancer samples. These data provide a catalog of miR genes that may have roles in cancer and argue that the full complement of miRs in a genome may be extensively involved in cancers.
Footnotes
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↵ ¶ To whom correspondence should be addressed at: Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University, 233 South 10th Street, Philadelphia, PA 19107. E-mail: carlo.croce{at}mail.tju.edu.
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↵ † G.A.C. and C.S. contributed equally to this work.
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Abbreviations: miR, microRNA; B-CLL, B cell chronic lymphocytic leukemias; LOH, loss of heterozygosity; CAGR, cancer-associated genomic region; IRR, incidence rate ratio; TS, tumor suppressor; FRA, fragile site; HPV, human papilloma virus; OG, oncogene; HD, homozygous deletion; HOX, homeobox.
- Copyright © 2004, The National Academy of Sciences
Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers
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