{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T02:07:15Z","timestamp":1790129235171,"version":"4.0.1"},"reference-count":59,"publisher":"National Academy of Sciences","issue":"5","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2016,2,2]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>The clinical and scientific community widely regards uterine leiomyomas as a single entity, although evidence of genetic heterogeneity exists. The aim of this study was to explore transcriptional differences between leiomyomas harboring different genetic alterations, including high mobility group AT-hook 2 rearrangements, mediator complex subunit 12 mutations, biallelic inactivation of fumarate hydratase, and collagen, type IV, alpha 5-collagen, type IV, alpha 6 deletions. The evidence presented herein strongly suggests that specific driver mutations are the major determinants of expression changes in leiomyomas. Here we highlight subtype-specific expression differences in key driver pathways and emphasize the utility of stratification in leiomyoma research. Finally, we offer a set of candidate biomarkers that will facilitate the molecular classification of leiomyomas.<\/jats:p>","DOI":"10.1073\/pnas.1518752113","type":"journal-article","created":{"date-parts":[[2016,2,2]],"date-time":"2016-02-02T15:22:15Z","timestamp":1454426535000},"page":"1315-1320","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":211,"title":["Integrated data analysis reveals uterine leiomyoma subtypes with distinct driver pathways and biomarkers"],"prefix":"10.1073","volume":"113","author":[{"given":"Miika","family":"Mehine","sequence":"first","affiliation":[{"name":"Medicum, Department of Medical and Clinical Genetics, University of Helsinki, Helsinki FIN-00014, Finland;"},{"name":"Research Programs Unit, Genome-Scale Biology, University of Helsinki, Helsinki FIN-00014, Finland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eevi","family":"Kaasinen","sequence":"additional","affiliation":[{"name":"Medicum, Department of Medical and Clinical Genetics, University of Helsinki, Helsinki FIN-00014, Finland;"},{"name":"Research Programs Unit, Genome-Scale Biology, University of Helsinki, Helsinki FIN-00014, Finland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna-Riikka","family":"Heinonen","sequence":"additional","affiliation":[{"name":"Medicum, Department of Medical and Clinical Genetics, University of Helsinki, Helsinki FIN-00014, Finland;"},{"name":"Research Programs Unit, Genome-Scale Biology, University of Helsinki, Helsinki FIN-00014, Finland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Netta","family":"M\u00e4kinen","sequence":"additional","affiliation":[{"name":"Medicum, Department of Medical and Clinical Genetics, University of Helsinki, Helsinki FIN-00014, Finland;"},{"name":"Research Programs Unit, Genome-Scale Biology, University of Helsinki, Helsinki FIN-00014, Finland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kati","family":"K\u00e4mpj\u00e4rvi","sequence":"additional","affiliation":[{"name":"Medicum, Department of Medical and Clinical Genetics, University of Helsinki, Helsinki FIN-00014, Finland;"},{"name":"Research Programs Unit, Genome-Scale Biology, University of Helsinki, Helsinki FIN-00014, Finland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanna","family":"Sarvilinna","sequence":"additional","affiliation":[{"name":"Research Programs Unit, Genome-Scale Biology, University of Helsinki, Helsinki FIN-00014, Finland;"},{"name":"Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki FIN-00029, Finland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mervi","family":"Aavikko","sequence":"additional","affiliation":[{"name":"Medicum, Department of Medical and Clinical Genetics, University of Helsinki, Helsinki FIN-00014, Finland;"},{"name":"Research Programs Unit, Genome-Scale Biology, University of Helsinki, Helsinki FIN-00014, Finland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"V\u00e4h\u00e4rautio","sequence":"additional","affiliation":[{"name":"Research Programs Unit, Genome-Scale Biology, University of Helsinki, Helsinki FIN-00014, Finland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annukka","family":"Pasanen","sequence":"additional","affiliation":[{"name":"Department of Pathology and HUSLAB, Helsinki University Hospital, University of Helsinki, Helsinki FIN-00014, Finland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"B\u00fctzow","sequence":"additional","affiliation":[{"name":"Department of Pathology and HUSLAB, Helsinki University Hospital, University of Helsinki, Helsinki FIN-00014, Finland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oskari","family":"Heikinheimo","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki FIN-00029, Finland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jari","family":"Sj\u00f6berg","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki FIN-00029, Finland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esa","family":"Pitk\u00e4nen","sequence":"additional","affiliation":[{"name":"Medicum, Department of Medical and Clinical Genetics, University of Helsinki, Helsinki FIN-00014, Finland;"},{"name":"Research Programs Unit, Genome-Scale Biology, University of Helsinki, Helsinki FIN-00014, Finland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pia","family":"Vahteristo","sequence":"additional","affiliation":[{"name":"Medicum, Department of Medical and Clinical Genetics, University of Helsinki, Helsinki FIN-00014, Finland;"},{"name":"Research Programs Unit, Genome-Scale Biology, University of Helsinki, Helsinki FIN-00014, Finland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauri A.","family":"Aaltonen","sequence":"additional","affiliation":[{"name":"Medicum, Department of Medical and Clinical Genetics, University of Helsinki, Helsinki FIN-00014, Finland;"},{"name":"Research Programs Unit, Genome-Scale Biology, University of Helsinki, Helsinki FIN-00014, Finland;"},{"name":"Department of Biosciences and Nutrition, Karolinska Institutet, SE-171 77, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2016,1,19]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1542-2011.2012.00176.x"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.rbmo.2013.04.001"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1208930"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1302736"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2014.06.050"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cancergencyto.2010.08.005"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.27424"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-4608(91)90229-N"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1208784"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cancergencyto.2009.03.011"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2014.01.011"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-4608(96)00406-2"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv177"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deh698"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi431"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.20291"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2005.12.059"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-4471"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0012362"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds051"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-0541"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-06-0331"},{"key":"e_1_3_3_23_2","first-page":"106","article-title":"PLAG1, the main translocation target in pleomorphic adenoma of the salivary glands, is a positive regulator of IGF-II","volume":"60","author":"Voz ML","year":"2000","unstructured":"ML Voz, NS Agten, WJ Van de Ven, K Kas, PLAG1, the main translocation target in pleomorphic adenoma of the salivary glands, is a positive regulator of IGF-II. Cancer Res 60, 106\u2013113 (2000).","journal-title":"Cancer Res"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1207013"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2012.1641"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-2277"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.3835"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq212"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2011.08.024"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2011.09.006"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2012.05.016"},{"key":"e_1_3_3_32_2","first-page":"289","article-title":"The HMGA proteins: A myriad of functions (Review)","volume":"32","author":"Cleynen I","year":"2008","unstructured":"I Cleynen, WJ Van de Ven, The HMGA proteins: A myriad of functions (Review). Int J Oncol 32, 289\u2013305 (2008).","journal-title":"Int J Oncol"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2014.01.017"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1313650110"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0040015"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.20402"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1043-2760(02)00603-3"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205428"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/30515"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1215759110"},{"key":"e_1_3_3_41_2","first-page":"765","article-title":"PLAG1, the prototype of the PLAG gene family: Versatility in tumour development (review)","volume":"30","author":"Van Dyck F","year":"2007","unstructured":"F Van Dyck, J Declercq, CV Braem, WJ Van de Ven, PLAG1, the prototype of the PLAG gene family: Versatility in tumour development (review). Int J Oncol 30, 765\u2013774 (2007).","journal-title":"Int J Oncol"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.10307"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1111\/his.12152"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cancergen.2013.05.019"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.2042311"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.9.9.2383"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1111\/ijlh.12057"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.5732\/cjc.011.10405"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.44.31179"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10689-011-9428-z"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2011.10.005"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3278"},{"key":"e_1_3_3_53_2","first-page":"1351","article-title":"Fusion transcripts involving HMGA2 are not a common molecular mechanism in uterine leiomyomata with rearrangements in 12q15","volume":"63","author":"Quade BJ","year":"2003","unstructured":"BJ Quade, , Fusion transcripts involving HMGA2 are not a common molecular mechanism in uterine leiomyomata with rearrangements in 12q15. Cancer Res 63, 1351\u20131358 (2003).","journal-title":"Cancer Res"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.22001"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0215(200002)9999:9999<::AID-IJC1050>3.0.CO;2-1"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-04-426965"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000000110"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3335"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp120"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1518752113","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T01:27:20Z","timestamp":1649813240000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1518752113"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,1,19]]},"references-count":59,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2016,2,2]]}},"alternative-id":["10.1073\/pnas.1518752113"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1518752113","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.726086970.793517274","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.726086970.793517048","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,1,19]]},"assertion":[{"value":"2016-01-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}