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Endometrial carcinoma is divided into two main histological types, type I or endometrioid and type II or non\u2010endometrioid, each of which have characteristic, although not exclusive, molecular alterations and mutational profiles. Nevertheless, information about the implication and relevance of some of these genes in this disease is lacking. We sought here to identify new recurrently mutated genes in endometrioid cancers that play a role in tumourigenesis and that influence the clinical outcome. We focused on low\u2010grade, non\u2010ultramutated tumours as these tumours have a worse prognosis than the ultramutated <jats:italic>POLE<\/jats:italic>\u2010positive endometrioid endometrial carcinomas (EECs). We performed exome\u2010sequencing of 11 EECs with matched normal tissue and subsequently validated 15 candidate genes in 76 samples. For the first time, we show that mutations in chromatin remodelling\u2010related genes (<jats:italic>KMT2D<\/jats:italic>, <jats:italic>KMT2C<\/jats:italic>, <jats:italic>SETD1B<\/jats:italic> and <jats:italic>BCOR<\/jats:italic>) and in DNA\u2010repair\u2010related genes (<jats:italic>BRCA1<\/jats:italic>, <jats:italic>BRCA2<\/jats:italic>, <jats:italic>RAD50<\/jats:italic> and <jats:italic>CHD4<\/jats:italic>) are frequent in this subtype of endometrial cancer. The alterations to these genes occurred with frequencies ranging from 35.5% for <jats:italic>KMT2D<\/jats:italic> to 10.5% for <jats:italic>BRCA1<\/jats:italic> and <jats:italic>BCOR<\/jats:italic>, with some showing a tendency toward co\u2010occurrence (<jats:italic>RAD50<\/jats:italic>\u2010<jats:italic>KMT2D<\/jats:italic> and <jats:italic>RAD50\u2010SETD1B<\/jats:italic>). All these genes harboured specific mutational hotspots. In addition, the mutational status of <jats:italic>KMT2C<\/jats:italic>, <jats:italic>KMT2D<\/jats:italic> and <jats:italic>SETD1B<\/jats:italic> helps to predict the degree of myometrial invasion, a critical prognostic feature. These results highlight the possible implication of these genes in this disease, creating opportunities for new therapeutic approaches.<\/jats:p>","DOI":"10.1002\/ijc.30573","type":"journal-article","created":{"date-parts":[[2016,12,20]],"date-time":"2016-12-20T17:49:36Z","timestamp":1482256176000},"page":"1551-1563","source":"Crossref","is-referenced-by-count":38,"title":["Chromatin remodelling and DNA repair genes are frequently mutated in endometrioid endometrial carcinoma"],"prefix":"10.1002","volume":"140","author":[{"given":"Pablo","family":"Garc\u00eda\u2010Sanz","sequence":"first","affiliation":[{"name":"MD Anderson International Foundation Madrid Spain"},{"name":"Departamento de Bioqu\u00edmica Universidad Aut\u00f3noma de Madrid (UAM), Instituto de Investigaciones Biom\u00e9dicas \u201cAlberto Sols\u201d (CSIC\u2010UAM) Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan 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