DOI: 10.1073/pnas.0307323101. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers

Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers

10.1073/pnas.0307323101

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

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.

Bibliography

Calin, G. A., Sevignani, C., Dumitru, C. D., Hyslop, T., Noch, E., Yendamuri, S., Shimizu, M., Rattan, S., Bullrich, F., Negrini, M., & Croce, C. M. (2004). Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proceedings of the National Academy of Sciences, 101(9), 2999â3004.

Authors 11

George Adrian Calin (first)
Cinzia Sevignani (additional)
Calin Dan Dumitru (additional)
Terry Hyslop (additional)
Evan Noch (additional)
Sai Yendamuri (additional)
Masayoshi Shimizu (additional)
Sashi Rattan (additional)
Florencia Bullrich (additional)
Massimo Negrini (additional)
Carlo M. Croce (additional)

References 50 Referenced 3,157

10.1016/S1367-5931(03)00075-9
Moss E. G. (2003) MicroRNAs in Noncoding RNAs: Molecular Biology and Molecular Medicine (Eurekah.com) pp. 98-114.
10.1038/35040556
10.1016/S0092-8674(03)00428-8
10.1016/S0960-9822(03)00250-1
10.1016/S0092-8674(03)00231-9
10.1016/S0168-9525(01)02624-5
10.1038/ng865
10.1073/pnas.242606799
Bullrich F. & Croce C. M. (2001) Chronic Lymphoid Leukemia (Dekker New York).
10.1126/science.1080372
10.1126/science.1064921
10.1126/science.1065062
10.1126/science.1065329
10.1101/gad.974702
10.1016/S0960-9822(02)00809-6
10.1261/rna.2141503
10.1016/S1534-5807(03)00227-2
10.1016/S0092-8674(00)81034-X
10.1073/pnas.191175898
10.1073/pnas.0931262100
10.1159/000072843
10.1016/S0168-9525(01)02303-4
Thorland, E. C., Myers, S. L., Persing, D. H., Sarkar, G., McGovern, R. M., Gostout, B. S. & Smith, D. I. (2000) Cancer Res. 60, 5916-5921.11085503 / Cancer Res. (2000)
10.1038/sj.onc.1206170
Simoneau, M., Aboulkassim, T. O., LaRue, H., Rousseau, F. & Fradet, Y. (1999) Oncogene 7, 157-163. / Oncogene (1999)
di Iasio, M. G., Calin, G. A., Tibiletti, M. G., Vorechovsky, I., Benediktsson, K. P., Taramelli, R., Barbanti-Brodano, G. & Negrini, M. (1999) Oncogene 25, 1635-1638. / Oncogene (1999)
10.1126/science.282.5387.284
10.1016/S0304-3835(02)00622-5
10.1111/j.1349-7006.2000.tb00986.x
10.1146/annurev.genet.32.1.7
10.1038/sj.onc.1205835
Etiemble, J., Moroy, T., Jacquemin, E., Tiollais, P. & Buendia, M. A. (1989) Oncogene 4, 51-57.2644611 / Oncogene (1989)
10.1182/blood-2002-10-3236
10.1038/nature01278
10.1006/excr.1999.4451
10.1634/stemcells.20-5-364
10.1016/S0960-9822(00)00676-X
Michael, M. Z., O' Connor, S. M., van Holst Pellekaan, N. G., Young, G. P. & James, R. J. (2003) Mol. Cancer Res. 1, 882-891.14573789 / Mol. Cancer Res. (2003)
10.1073/pnas.86.22.8867
10.1016/S0378-1119(01)00612-6
10.1016/S0014-5793(96)01365-8
10.1006/jmbi.1994.1116
10.1016/S0888-7543(03)00129-0
10.1126/science.1073827
10.1101/gad.1026102
10.1016/S1044-579X(03)00038-5
Calin, G. (1994) Oncol. Rep. 1, 987-991. / Oncol. Rep. (1994)
10.1038/ng721
10.1002/gcc.10316

Dates

Type	When
Created	21 years, 6 months ago (March 2, 2004, 9:33 p.m.)
Deposited	3 years, 4 months ago (April 25, 2022, 10:40 p.m.)
Indexed	2 days, 12 hours ago (Sept. 3, 2025, 6:29 a.m.)
Issued	21 years, 6 months ago (Feb. 18, 2004)
Published	21 years, 6 months ago (Feb. 18, 2004)
Published Online	21 years, 6 months ago (Feb. 18, 2004)
Published Print	21 years, 6 months ago (March 2, 2004)

Funders 0

None

BibTeX

@article{Calin_2004, title={Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers}, volume={101}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0307323101}, DOI={10.1073/pnas.0307323101}, number={9}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Calin, George Adrian and Sevignani, Cinzia and Dumitru, Calin Dan and Hyslop, Terry and Noch, Evan and Yendamuri, Sai and Shimizu, Masayoshi and Rattan, Sashi and Bullrich, Florencia and Negrini, Massimo and Croce, Carlo M.}, year={2004}, month=feb, pages={2999–3004} }

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