{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T22:00:57Z","timestamp":1783116057365,"version":"3.54.6"},"reference-count":26,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,8,29]],"date-time":"2013-08-29T00:00:00Z","timestamp":1377734400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2014,2]]},"abstract":"<jats:p>Uterine leiomyomas are extremely common tumors originating from the smooth muscle cells of myometrium. We recently reported recurrent somatic mutations in mediator complex subunit 12 (<jats:italic>MED12<\/jats:italic>) in the majority of these lesions, and analyzed chromosomal abnormalities in leiomyomas by whole\u2010genome sequencing. The aim of our study was to examine in detail uterine leiomyoma exomes, to search for driver mutations in <jats:italic>MED12<\/jats:italic> mutation\u2010negative leiomyomas and to scrutinize <jats:italic>MED12<\/jats:italic> mutation\u2010positive leimyomas for additional contributing mutations. We analyzed whole exome sequencing data of 27 uterine leiomyomas (12 <jats:italic>MED12<\/jats:italic> mutation\u2010negative and 15 <jats:italic>MED12<\/jats:italic> mutation\u2010positive) and their paired normal myometrium. We searched for genes, which would be recurrently mutated. No such genes were identified in <jats:italic>MED12<\/jats:italic> mutation\u2010negative uterine leiomyomas. Similarly, <jats:italic>MED12<\/jats:italic> mutation\u2010positive leiomyomas displayed no additional recurrent changes. The complete lack of novel driver point mutations in the examined series highlights the unique role of <jats:italic>MED12<\/jats:italic> mutations in genesis of uterine leiomyomas, and suggests that these mutations alone may be sufficient for tumor development. Additional factors that cannot be detected by exome sequencing, such as somatic structural rearrangements, epigenetic events and intronic variants, are likely to have a particular impact to the development of <jats:italic>MED12<\/jats:italic> wild\u2010type lesions.<\/jats:p>","DOI":"10.1002\/ijc.28410","type":"journal-article","created":{"date-parts":[[2013,8,3]],"date-time":"2013-08-03T06:38:46Z","timestamp":1375511926000},"page":"1008-1012","source":"Crossref","is-referenced-by-count":34,"title":["Exomic landscape of <i>MED12<\/i> mutation\u2010negative and \u2010positive uterine leiomyomas"],"prefix":"10.1002","volume":"134","author":[{"given":"Netta","family":"M\u00e4kinen","sequence":"first","affiliation":[{"name":"Department of Medical Genetics Genome\u2010Scale Biology Research Program University of Helsinki Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pia","family":"Vahteristo","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Genome\u2010Scale Biology Research Program University of Helsinki Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"B\u00fctzow","sequence":"additional","affiliation":[{"name":"Department of Pathology Haartman Institute and HUSLAB University of Helsinki and Helsinki University Central Hospital Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jari","family":"Sj\u00f6berg","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Helsinki University Central Hospital Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauri A.","family":"Aaltonen","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Genome\u2010Scale Biology Research Program University of Helsinki Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,8,29]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1067\/mob.2003.99"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)03622-9"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.2870020103"},{"key":"e_1_2_6_5_1","first-page":"923","article-title":"Cytogenetic abnormalities in uterine leiomyomata","volume":"77","author":"Rein MS","year":"1991","journal-title":"Obstet Gynecol"},{"key":"e_1_2_6_6_1","first-page":"209","article-title":"Uterine leiomyomas: cytogenetic and histologic profile","volume":"80","author":"Meloni AM","year":"1992","journal-title":"Obstet Gynecol"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng849"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1208930"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2005.03.009"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2010.02.004"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1302736"},{"key":"e_1_2_6_12_1","first-page":"233","volume-title":"World health organization classification of tumours: tumours of the breast and female genital organs","author":"Hendrickson MR","year":"2003"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.107524.110"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq330"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.051633798"},{"key":"e_1_2_6_17_1","first-page":"4554","article-title":"Few FH mutations in sporadic counterparts of tumor types observed in hereditary leiomyomatosis and renal cell cancer families","volume":"62","author":"Kiuru M","year":"2002","journal-title":"Cancer Res"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2013.33"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10689-011-9428-z"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2264(199908)25:4<316::AID-GCC2>3.0.CO;2-0"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.10240"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.27424"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-4608(99)00070-9"},{"key":"e_1_2_6_24_1","first-page":"19","article-title":"Allelic knockout of novel splice variants of human recombination repair gene RAD51B in t(12;14) uterine leiomyomas","volume":"59","author":"Schoenmakers EF","year":"1999","journal-title":"Cancer Res"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/1098-2264(200007)28:3<235::AID-GCC1>3.0.CO;2-7"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-4608(96)00406-2"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1054"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fijc.28410","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fijc.28410","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.28410","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T19:50:47Z","timestamp":1696362647000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.28410"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,8,29]]},"references-count":26,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2014,2]]}},"alternative-id":["10.1002\/ijc.28410"],"URL":"https:\/\/doi.org\/10.1002\/ijc.28410","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,8,29]]}}}