Human MicroRNA Genes Are Frequently Located at Fragile Sites and Genomic Regions Involved in Cancers

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2004 Feb 20

PMID 14973191

Citations 1777

Authors

George Adrian Calin

Cinzia Sevignani

Calin Dan Dumitru

Terry Hyslop

Evan Noch

Sai Yendamuri

Masayoshi Shimizu

Sashi Rattan

Florencia Bullrich

Massimo Negrini

Carlo M Croce

Affiliations

Soon will be listed here.

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.

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