{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T20:06:01Z","timestamp":1789934761622,"version":"4.0.1"},"reference-count":50,"publisher":"National Academy of Sciences","issue":"9","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2004,3,2]]},"abstract":"<jats:p>\n                    A large number of tiny noncoding RNAs have been cloned and named microRNAs (miRs). Recently, we have reported that\n                    <jats:italic>miR-15a<\/jats:italic>\n                    and\n                    <jats:italic>miR-16a<\/jats:italic>\n                    , 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.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0307323101","type":"journal-article","created":{"date-parts":[[2004,3,2]],"date-time":"2004-03-02T21:33:11Z","timestamp":1078263191000},"page":"2999-3004","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":3198,"title":["Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers"],"prefix":"10.1073","volume":"101","author":[{"given":"George Adrian","family":"Calin","sequence":"first","affiliation":[{"name":"Departments of Microbiology and Immunology and Medicine, Division of Clinical Pharmacology, Biostatistics Section, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107; and Dipartimento di Medicina Sperimentale e Diagnostica e Centro Interdipartimentale per la Ricerca sul Cancro, Universit\u00e0 di Ferrara, Ferrara 44100, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinzia","family":"Sevignani","sequence":"additional","affiliation":[{"name":"Departments of Microbiology and Immunology and Medicine, Division of Clinical Pharmacology, Biostatistics Section, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107; and Dipartimento di Medicina Sperimentale e Diagnostica e Centro Interdipartimentale per la Ricerca sul Cancro, Universit\u00e0 di Ferrara, Ferrara 44100, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Calin Dan","family":"Dumitru","sequence":"additional","affiliation":[{"name":"Departments of Microbiology and Immunology and Medicine, Division of Clinical Pharmacology, Biostatistics Section, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107; and Dipartimento di Medicina Sperimentale e Diagnostica e Centro Interdipartimentale per la Ricerca sul Cancro, Universit\u00e0 di Ferrara, Ferrara 44100, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terry","family":"Hyslop","sequence":"additional","affiliation":[{"name":"Departments of Microbiology and Immunology and Medicine, Division of Clinical Pharmacology, Biostatistics Section, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107; and Dipartimento di Medicina Sperimentale e Diagnostica e Centro Interdipartimentale per la Ricerca sul Cancro, Universit\u00e0 di Ferrara, Ferrara 44100, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan","family":"Noch","sequence":"additional","affiliation":[{"name":"Departments of Microbiology and Immunology and Medicine, Division of Clinical Pharmacology, Biostatistics Section, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107; and Dipartimento di Medicina Sperimentale e Diagnostica e Centro Interdipartimentale per la Ricerca sul Cancro, Universit\u00e0 di Ferrara, Ferrara 44100, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sai","family":"Yendamuri","sequence":"additional","affiliation":[{"name":"Departments of Microbiology and Immunology and Medicine, Division of Clinical Pharmacology, Biostatistics Section, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107; and Dipartimento di Medicina Sperimentale e Diagnostica e Centro Interdipartimentale per la Ricerca sul Cancro, Universit\u00e0 di Ferrara, Ferrara 44100, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayoshi","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Departments of Microbiology and Immunology and Medicine, Division of Clinical Pharmacology, Biostatistics Section, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107; and Dipartimento di Medicina Sperimentale e Diagnostica e Centro Interdipartimentale per la Ricerca sul Cancro, Universit\u00e0 di Ferrara, Ferrara 44100, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sashi","family":"Rattan","sequence":"additional","affiliation":[{"name":"Departments of Microbiology and Immunology and Medicine, Division of Clinical Pharmacology, Biostatistics Section, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107; and Dipartimento di Medicina Sperimentale e Diagnostica e Centro Interdipartimentale per la Ricerca sul Cancro, Universit\u00e0 di Ferrara, Ferrara 44100, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florencia","family":"Bullrich","sequence":"additional","affiliation":[{"name":"Departments of Microbiology and Immunology and Medicine, Division of Clinical Pharmacology, Biostatistics Section, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107; and Dipartimento di Medicina Sperimentale e Diagnostica e Centro Interdipartimentale per la Ricerca sul Cancro, Universit\u00e0 di Ferrara, Ferrara 44100, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Negrini","sequence":"additional","affiliation":[{"name":"Departments of Microbiology and Immunology and Medicine, Division of Clinical Pharmacology, Biostatistics Section, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107; and Dipartimento di Medicina Sperimentale e Diagnostica e Centro Interdipartimentale per la Ricerca sul Cancro, Universit\u00e0 di Ferrara, Ferrara 44100, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo M.","family":"Croce","sequence":"additional","affiliation":[{"name":"Departments of Microbiology and Immunology and Medicine, Division of Clinical Pharmacology, Biostatistics Section, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107; and Dipartimento di Medicina Sperimentale e Diagnostica e Centro Interdipartimentale per la Ricerca sul Cancro, Universit\u00e0 di Ferrara, Ferrara 44100, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2004,2,18]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1367-5931(03)00075-9"},{"key":"e_1_3_2_2_2","unstructured":"Moss E. G. (2003) MicroRNAs in Noncoding RNAs: Molecular Biology and Molecular Medicine (Eurekah.com) pp. 98-114."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/35040556"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00428-8"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(03)00250-1"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00231-9"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9525(01)02624-5"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng865"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.242606799"},{"key":"e_1_3_2_10_2","unstructured":"Bullrich F. & Croce C. M. (2001) Chronic Lymphoid Leukemia (Dekker New York)."},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1080372"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1064921"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1065062"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1065329"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.974702"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(02)00809-6"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1261\/rna.2141503"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(03)00227-2"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81034-X"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.191175898"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0931262100"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1159\/000072843"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9525(01)02303-4"},{"key":"e_1_3_2_24_2","first-page":"5916","volume":"60","year":"2000","unstructured":"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","journal-title":"Cancer Res."},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1206170"},{"key":"e_1_3_2_26_2","first-page":"157","volume":"7","year":"1999","unstructured":"Simoneau, M., Aboulkassim, T. O., LaRue, H., Rousseau, F. & Fradet, Y. (1999) Oncogene 7, 157-163.","journal-title":"Oncogene"},{"key":"e_1_3_2_27_2","first-page":"1635","volume":"25","year":"1999","unstructured":"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.","journal-title":"Oncogene"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.282.5387.284"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3835(02)00622-5"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2000.tb00986.x"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genet.32.1.7"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205835"},{"key":"e_1_3_2_33_2","first-page":"51","volume":"4","year":"1989","unstructured":"Etiemble, J., Moroy, T., Jacquemin, E., Tiollais, P. & Buendia, M. A. (1989) Oncogene 4, 51-57.2644611","journal-title":"Oncogene"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-10-3236"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01278"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1006\/excr.1999.4451"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.20-5-364"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(00)00676-X"},{"key":"e_1_3_2_39_2","first-page":"882","volume":"1","year":"2003","unstructured":"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","journal-title":"Mol. Cancer Res."},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.22.8867"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(01)00612-6"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(96)01365-8"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1994.1116"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0888-7543(03)00129-0"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1073827"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1026102"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1044-579X(03)00038-5"},{"key":"e_1_3_2_48_2","first-page":"987","volume":"1","year":"1994","unstructured":"Calin, G. (1994) Oncol. Rep. 1, 987-991.","journal-title":"Oncol. Rep."},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng721"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.10316"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0307323101","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,25]],"date-time":"2022-04-25T22:40:42Z","timestamp":1650926442000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0307323101"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,2,18]]},"references-count":50,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2004,3,2]]}},"alternative-id":["10.1073\/pnas.0307323101"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0307323101","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,2,18]]},"assertion":[{"value":"2004-02-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}