{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T20:16:44Z","timestamp":1790108204488,"version":"4.0.1"},"reference-count":71,"publisher":"Cold Spring Harbor Laboratory","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cold Spring Harb Mol Case Stud"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:p>We describe a woman with the known pathogenic germline variant<jats:italic>CHEK2<\/jats:italic>:c.1100delC and synchronous diagnoses of both pelvic genital type leiomyosarcoma (LMS) and metastatic invasive ductal breast carcinoma.<jats:italic>CHEK2<\/jats:italic>(checkpoint kinase 2) is a tumor-suppressor gene encoding a serine\/threonine-protein kinase (CHEK2) involved in double-strand DNA break repair and cell cycle arrest. The<jats:italic>CHEK2<\/jats:italic>:c.1100delC variant is a moderate penetrance allele resulting in an approximately twofold increase in breast cancer risk. Whole-genome and whole-transcriptome sequencing were performed on the leiomyosarcoma and matched blood-derived DNA. Despite the presence of several genomic hits within the double-strand DNA damage pathway (<jats:italic>CHEK2<\/jats:italic>germline variant and multiple<jats:italic>RAD51B<\/jats:italic>somatic structural variants), tumor profiling did not show an obvious DNA repair deficiency signature. However, even though the LMS displayed clear malignant features, its genomic profiling revealed several characteristics classically associated with leiomyomas including a translocation, t(12;14), with one breakpoint disrupting<jats:italic>RAD51B<\/jats:italic>and the other breakpoint upstream of<jats:italic>HMGA2<\/jats:italic>with very high expression of<jats:italic>HMGA2<\/jats:italic>and<jats:italic>PLAG1<\/jats:italic>. This is the first report of LMS genomic profiling in a patient with the germline<jats:italic>CHEK2<\/jats:italic>:c.1100delC variant and an additional diagnosis of metastatic invasive ductal breast carcinoma. We also describe a possible mechanistic relationship between leiomyoma and LMS based on genomic and transcriptome data. Our findings suggest that<jats:italic>RAD51B<\/jats:italic>translocation and<jats:italic>HMGA2<\/jats:italic>overexpression may play an important role in LMS oncogenesis.<\/jats:p>","DOI":"10.1101\/mcs.a001628","type":"journal-article","created":{"date-parts":[[2017,5,17]],"date-time":"2017-05-17T00:40:56Z","timestamp":1494981656000},"page":"a001628","source":"Crossref","is-referenced-by-count":13,"title":["Genomic profiling of pelvic genital type leiomyosarcoma in a woman with a germline<i>CHEK2<\/i>:c.1100delC mutation and a concomitant diagnosis of metastatic invasive ductal breast carcinoma"],"prefix":"10.1101","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2600-1197","authenticated-orcid":false,"given":"My Linh","family":"Thibodeau","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caralyn","family":"Reisle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1277-6335","authenticated-orcid":false,"given":"Eric","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee Ann","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yazeed","family":"Alwelaie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen L.","family":"Mungall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn","family":"Ch'ng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony","family":"Ng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Yip","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard","family":"J. 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