{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T17:19:41Z","timestamp":1793380781700,"version":"4.5.0"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,12,15]],"date-time":"2020-12-15T00:00:00Z","timestamp":1607990400000},"content-version":"vor","delay-in-days":14,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2017R1A2B2002314"],"award-info":[{"award-number":["2017R1A2B2002314"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2017R1E1A1A01074913"],"award-info":[{"award-number":["2017R1E1A1A01074913"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2019R1C1C1004909"],"award-info":[{"award-number":["2019R1C1C1004909"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Exp Mol Med"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Little is known about genomic alterations of gestational choriocarcinoma (GC), unique cancer that originates in pregnant tissues, and the progression mechanisms from the nonmalignant complete hydatidiform mole (CHM) to GC. Whole-exome sequencing (20 GCs) and\/or single-nucleotide polymorphism microarray (29 GCs) were performed. We analyzed copy-neutral loss-of-heterozygosity (CN-LOH) in 29 GCs that exhibited androgenetic CN-LOHs (20 monospermic, 8 dispermic) and no CN-LOH (one with <jats:italic>NLRP7<\/jats:italic> mutation). Most GCs (25\/29) harboring recurrent copy number alterations (CNAs) and gains on 1q21.1-q44 were significantly associated with poor prognosis. We detected five driver mutations in the GCs, most of which were chromatin remodeling gene (<jats:italic>ARID1A<\/jats:italic>, <jats:italic>SMARCD1<\/jats:italic>, and <jats:italic>EP300<\/jats:italic>) mutations but not in common cancer genes such as <jats:italic>TP53<\/jats:italic> and <jats:italic>KRAS<\/jats:italic>. One patient\u2019s serial CHM\/invasive mole\/GC showed consistent CN-LOHs, but only the GC harbored CNAs, indicating that CN-LOH is an early pivotal event in HM-IM-GC development, and CNAs may be a late event that promotes CHM progression to GC. Our data indicate that GCs have unique profiles of CN-LOHs, mutations and CNAs that together differentiate GCs from non-GCs. Practically, CN-LOH and CNA profiles are useful for the molecular diagnosis of GC and the selection of GC patients with poor prognosis for more intensive treatments, respectively.<\/jats:p>","DOI":"10.1038\/s12276-020-00544-0","type":"journal-article","created":{"date-parts":[[2020,12,15]],"date-time":"2020-12-15T07:03:18Z","timestamp":1608015798000},"page":"2046-2054","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Distinct genomic profiles of gestational choriocarcinoma, a unique cancer of pregnant tissues"],"prefix":"10.1038","volume":"52","author":[{"given":"Seung-Hyun","family":"Jung","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youn Jin","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min Sung","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeon-Chun","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi-Ryung","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo Young","family":"Hur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ah Won","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ok Ran","family":"Shin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeana","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung Hak","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7816-1299","authenticated-orcid":false,"given":"Dongwan","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Yong","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeun-Jun","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sug Hyung","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,12,15]]},"reference":[{"key":"544_CR1","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1016\/S0140-6736(10)60280-2","volume":"376","author":"MJ Seckl","year":"2010","unstructured":"Seckl, M. J., Sebire, N. J. & Berkowitz, R. S. Gestational trophoblastic disease. Lancet 376, 717\u2013729 (2010).","journal-title":"Lancet"},{"key":"544_CR2","doi-asserted-by":"publisher","DOI":"10.1007\/s11912-014-0408-y","volume":"16","author":"FE Froeling","year":"2014","unstructured":"Froeling, F. E. & Seckl, M. J. Gestational trophoblastic tumours: an update for 2014. Curr. Oncol. Rep. 16, 408 (2014).","journal-title":"Curr. Oncol. Rep."},{"key":"544_CR3","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1097\/01.pap.0000163960.11107.73","volume":"12","author":"P Hui","year":"2005","unstructured":"Hui, P., Martel, M. & Parkash, V. Gestational trophoblastic diseases: recent advances in histopathologic diagnosis and related genetic aspects. Adv. Anat. Pathol. 12, 116\u2013125 (2005).","journal-title":"Adv. Anat. Pathol."},{"key":"544_CR4","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1038\/268633a0","volume":"268","author":"T Kajii","year":"1977","unstructured":"Kajii, T. & Ohama, K. Androgenetic origin of hydatidiform mole. Nature 268, 633\u2013634 (1977).","journal-title":"Nature"},{"key":"544_CR5","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1097\/PAS.0b013e3181520034","volume":"32","author":"C Bifulco","year":"2008","unstructured":"Bifulco, C. et al. Genotypic analysis of hydatidiform mole: an accurate and practical method of diagnosis. Am. J. Surg. Pathol. 32, 445\u2013451 (2008).","journal-title":"Am. J. Surg. Pathol."},{"key":"544_CR6","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1097\/PAS.0b013e318191f309","volume":"33","author":"TG McConnell","year":"2009","unstructured":"McConnell, T. G., Murphy, K. M., Hafez, M., Vang, R. & Ronnett, B. M. Diagnosis and subclassification of hydatidiform moles using p57 immunohistochemistry and molecular genotyping: validation and prospective analysis in routine and consultation practice settings with development of an algorithmic approach. Am. J. Surg. Pathol. 33, 805\u2013817 (2009).","journal-title":"Am. J. Surg. Pathol."},{"key":"544_CR7","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.ajog.2010.06.072","volume":"204","author":"JR Lurain","year":"2011","unstructured":"Lurain, J. R. Gestational trophoblastic disease II: classification and management of gestational trophoblastic neoplasia. Am. J. Obstet. Gynecol. 204, 11\u201318 (2011).","journal-title":"Am. J. Obstet. Gynecol."},{"key":"544_CR8","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1016\/j.ygyno.2008.09.005","volume":"112","author":"RS Berkowitz","year":"2009","unstructured":"Berkowitz, R. S. & Goldstein, D. P. Current management of gestational trophoblastic diseases. Gynecol. Oncol. 112, 654\u2013662 (2009).","journal-title":"Gynecol. Oncol."},{"key":"544_CR9","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.ygyno.2005.12.045","volume":"102","author":"LA Cole","year":"2006","unstructured":"Cole, L. A. et al. Gestational trophoblastic diseases: 2. Hyperglycosylated hCG as a reliable marker of active neoplasia. Gynecol. Oncol. 102, 151\u2013159 (2006).","journal-title":"Gynecol. Oncol."},{"key":"544_CR10","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1038\/ng.3343","volume":"47","author":"MD Stachler","year":"2015","unstructured":"Stachler, M. D. et al. Paired exome analysis of Barrett\u2019s esophagus and adenocarcinoma. Nat. Genet. 47, 1047\u20131055 (2015).","journal-title":"Nat. Genet."},{"key":"544_CR11","doi-asserted-by":"publisher","first-page":"1747","DOI":"10.1097\/PAS.0b013e31825ea736","volume":"36","author":"M Gupta","year":"2012","unstructured":"Gupta, M. et al. Diagnostic reproducibility of hydatidiform moles: ancillary techniques (p57 immunohistochemistry and molecular genotyping) improve morphologic diagnosis for both recently trained and experienced gynecologic pathologists. Am. J. Surg. Pathol. 36, 1747\u20131760 (2012).","journal-title":"Am. J. Surg. Pathol."},{"key":"544_CR12","first-page":"7049","volume":"11","author":"C Lazare","year":"2019","unstructured":"Lazare, C. et al. A pilot study comparing the genetic molecular biology of gestational and non-gestational choriocarcinoma. Am. J. Transl. Res. 11, 7049\u20137062 (2019).","journal-title":"Am. J. Transl. Res."},{"key":"544_CR13","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/0165-4608(89)90664-X","volume":"38","author":"U Surti","year":"1989","unstructured":"Surti, U. & Habibian, R. Chromosomal rearrangement in choriocarcinoma cell lines. Cancer Genet. Cytogenet. 38, 229\u2013240 (1989).","journal-title":"Cancer Genet. Cytogenet."},{"key":"544_CR14","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/S0165-4608(99)00103-X","volume":"116","author":"MN Ahmed","year":"2000","unstructured":"Ahmed, M. N., Kim, K., Haddad, B., Berchuck, A. & Qumsiyeh, M. B. Comparative genomic hybridization studies in hydatidiform moles and choriocarcinoma: amplification of 7q21-q31 and loss of 8p12-p21 in choriocarcinoma. Cancer Genet. Cytogenet. 116, 10\u201315 (2000).","journal-title":"Cancer Genet. Cytogenet."},{"key":"544_CR15","doi-asserted-by":"publisher","first-page":"2773","DOI":"10.1038\/sj.onc.1201461","volume":"15","author":"T Matsuda","year":"1997","unstructured":"Matsuda, T. et al. Human chromosome 7 carries a putative tumor suppressor gene(s) involved in choriocarcinoma. Oncogene 15, 2773\u20132781 (1997).","journal-title":"Oncogene"},{"key":"544_CR16","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.placenta.2016.12.009","volume":"50","author":"JB Mello","year":"2017","unstructured":"Mello, J. B. et al. Genomic profile in gestational and non-gestational choriocarcinomas. Placenta 50, 8\u201315 (2017).","journal-title":"Placenta"},{"key":"544_CR17","doi-asserted-by":"publisher","first-page":"1546","DOI":"10.1126\/science.1235122","volume":"339","author":"B Vogelstein","year":"2013","unstructured":"Vogelstein, B. et al. Cancer genome landscapes. Science 339, 1546\u20131558 (2013).","journal-title":"Science"},{"key":"544_CR18","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1053\/plac.2001.0744","volume":"23","author":"HW Li","year":"2002","unstructured":"Li, H. W., Tsao, S. W. & Cheung, A. N. Current understandings of the molecular genetics of gestational trophoblastic diseases. Placenta 23, 20\u201331 (2002).","journal-title":"Placenta"},{"key":"544_CR19","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1007\/s004280050253","volume":"433","author":"JY Lee","year":"1998","unstructured":"Lee, J. Y. et al. A simple, precise and economical microdissection technique for analysis of genomic DNA from archival tissue sections. Virchows Arch. 433, 305\u2013309 (1998).","journal-title":"Virchows Arch."},{"key":"544_CR20","doi-asserted-by":"publisher","first-page":"10672","DOI":"10.1073\/pnas.1606946113","volume":"113","author":"SH Jung","year":"2016","unstructured":"Jung, S. H. et al. Whole-exome sequencing identifies recurrent AKT1 mutations in sclerosing hemangioma of lung. Proc. Natl Acad. Sci. USA 113, 10672\u201310677 (2016).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"544_CR21","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/75556","volume":"25","author":"M Ashburner","year":"2000","unstructured":"Ashburner, M. et al. Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat. Genet. 25, 25\u201329 (2000).","journal-title":"Nat. Genet."},{"key":"544_CR22","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1038\/nbt.2514","volume":"31","author":"K Cibulskis","year":"2013","unstructured":"Cibulskis, K. et al. Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples. Nat. Biotechnol. 31, 213\u2013219 (2013).","journal-title":"Nat. Biotechnol."},{"key":"544_CR23","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1038\/ng.806","volume":"43","author":"MA DePristo","year":"2011","unstructured":"DePristo, M. A. et al. A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nat. Genet. 43, 491\u2013498 (2011).","journal-title":"Nat. Genet."},{"key":"544_CR24","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq603","volume":"38","author":"K Wang","year":"2010","unstructured":"Wang, K., Li, M. & Hakonarson, H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 38, e164 (2010).","journal-title":"Nucleic Acids Res."},{"key":"544_CR25","doi-asserted-by":"publisher","first-page":"242","DOI":"10.3389\/fimmu.2013.00242","volume":"4","author":"R Slim","year":"2013","unstructured":"Slim, R. & Wallace, E. P. NLRP7 and the genetics of hydatidiform moles: recent advances and new challenges. Front. Immunol. 4, 242 (2013).","journal-title":"Front. Immunol."},{"key":"544_CR26","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1038\/nrc1299","volume":"4","author":"PA Futreal","year":"2004","unstructured":"Futreal, P. A. et al. A census of human cancer genes. Nat. Rev. Cancer 4, 177\u2013183 (2004).","journal-title":"Nat. Rev. Cancer"},{"key":"544_CR27","first-page":"523","volume":"54","author":"JC Baltazar","year":"1976","unstructured":"Baltazar, J. C. Epidemiological features of choriocarcinoma. Bull. World Health Organ. 54, 523\u2013532 (1976).","journal-title":"Bull. World Health Organ."},{"key":"544_CR28","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1007\/BF00145384","volume":"8","author":"F Flam","year":"1992","unstructured":"Flam, F. & Rutqvist, L. E. Under-registration of gestational trophoblastic disease in the Swedish Cancer Registry. Eur. J. Epidemiol. 8, 683\u2013686 (1992).","journal-title":"Eur. J. Epidemiol."},{"key":"544_CR29","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.pharmthera.2018.05.001","volume":"190","author":"R Mathur","year":"2018","unstructured":"Mathur, R. ARID1A loss in cancer: towards a mechanistic understanding. Pharmacol. Therapeut. 190, 15\u201323 (2018).","journal-title":"Pharmacol. Therapeut."},{"key":"544_CR30","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1053\/j.seminoncol.2018.11.001","volume":"46","author":"W Stein","year":"2019","unstructured":"Stein, W. The ages of the cancer-associated genes. Semin. Oncol. 46, 10\u201318 (2019).","journal-title":"Semin. Oncol."},{"key":"544_CR31","doi-asserted-by":"publisher","first-page":"6718","DOI":"10.1158\/0008-5472.CAN-11-1562","volume":"71","author":"B Guan","year":"2011","unstructured":"Guan, B., Wang, T.-L. & Shih, I.-M. ARID1A, a factor that promotes formation of SWI\/SNF-mediated chromatin remodeling, is a tumor suppressor in gynecologic cancers. Cancer Res. 71, 6718\u20136727 (2011).","journal-title":"Cancer Res."}],"container-title":["Experimental &amp; Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/s12276-020-00544-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s12276-020-00544-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s12276-020-00544-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,20]],"date-time":"2023-05-20T21:11:31Z","timestamp":1684617091000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s12276-020-00544-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12]]},"references-count":31,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["544"],"URL":"https:\/\/doi.org\/10.1038\/s12276-020-00544-0","relation":{},"ISSN":["1226-3613","2092-6413"],"issn-type":[{"value":"1226-3613","type":"print"},{"value":"2092-6413","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12]]},"assertion":[{"value":"26 July 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 November 2020","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 November 2020","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 December 2020","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}