{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T04:36:00Z","timestamp":1789706160590,"version":"4.0.1"},"reference-count":52,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,9,20]],"date-time":"2021-09-20T00:00:00Z","timestamp":1632096000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1HD096147"],"award-info":[{"award-number":["RO1HD096147"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Adenomyosis and peritoneal endometriosis are common gynecologic lesions; they are characterized by aberrant locations of normal\u2010appearing endometrium in myometrium and peritoneal surface, respectively. Both ectopic lesions are speculated to originate from uterine eutopic endometrium, which is composed of epithelium and stroma, but how these two different tissue types co\u2010evolve in ectopic locations remains unclear. Here, we analyzed exome\u2010wide mutations and global methylation in microdissected epithelium and stroma separately in paired adenomyosis, peritoneal endometriosis, and endometrium to investigate their relationship. Analyses of somatic mutations and their allele frequencies indicate monoclonal development not only in epithelium but also in the stroma of adenomyosis and peritoneal endometriosis. Our preliminary phylogenetic study suggests a plausible clonal derivation in epithelium and stroma of both ectopic and eutopic endometrium from the same founder epithelium\u2010stroma progenitor cells. While a patient\u2010specific methylation landscape is evident, adenomyosis epithelium and stroma can be distinguished from normal\u2010appearing eutopic endometrium epigenetically. In summary, endometrial stroma, like its epithelial counterpart, could be clonal and both ectopic and eutopic endometrium following divergent evolutionary trajectories. Our data also warrant future investigations into the role of endometrial stroma in the pathobiology of endometrium\u2010related disorders. \u00a9 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.5778","type":"journal-article","created":{"date-parts":[[2021,8,16]],"date-time":"2021-08-16T04:47:31Z","timestamp":1629089251000},"page":"387-398","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Mutation and methylation profiles of ectopic and eutopic endometrial tissues"],"prefix":"10.1002","volume":"255","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7462-9870","authenticated-orcid":false,"given":"Lihong","family":"Li","sequence":"first","affiliation":[{"name":"Department of Gynecology and Obstetrics Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Facadio","family":"Antero","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Oncology Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Pathology Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamer","family":"Seckin","sequence":"additional","affiliation":[{"name":"Department of Gynecology Lenox Hill Hospital and Zucker School of Medicine at Hofstra\/Northwell  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayse","family":"Ayhan","sequence":"additional","affiliation":[{"name":"Department of Pathology Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5796-0836","authenticated-orcid":false,"given":"Thomas","family":"Pisanic","sequence":"additional","affiliation":[{"name":"Johns Hopkins Institute of NanoBio Technology Johns Hopkins University  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian\u2010Li","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics Johns Hopkins University School of Medicine  Baltimore MD USA"},{"name":"Department of Oncology Johns Hopkins University School of Medicine  Baltimore MD USA"},{"name":"Department of Pathology Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie","family":"Cope","sequence":"additional","affiliation":[{"name":"Department of Oncology Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Segars","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1084-2071","authenticated-orcid":false,"given":"Ie\u2010Ming","family":"Shih","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics Johns Hopkins University School of Medicine  Baltimore MD USA"},{"name":"Department of Oncology Johns Hopkins University School of Medicine  Baltimore MD USA"},{"name":"Department of Pathology Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,9,20]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0804690"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathmechdis-012419-032654"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0040-1718922"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0220256"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gyobfe.2015.09.001"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/09513590.2016.1232902"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/1933719116681515"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004347-200104000-00004"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2011.05.090"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmig.2015.09.018"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(72)90781-8"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2017.12.030"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2018.10.013"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43032-019-00127-z"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/des332"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2007.11.025"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejogrb.2008.12.010"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejogrb.2011.03.003"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.23736\/S0026-4946.20.05842-9"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13708-y"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1614814"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.5082"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4419-0489-8"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmig.2019.11.013"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.5219"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1754"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-019-0572-y"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-14701-6"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dez155"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.07.037"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2214-z"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.5314"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/d41586-020-01081-6"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2018-00281"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.00497"},{"key":"e_1_2_8_37_1","first-page":"784","article-title":"Novasoy and genistein inhibit endometrial cancer cell proliferation through disruption of the AKT\/mTOR and MAPK signaling pathways","volume":"10","author":"Malloy KM","year":"2018","journal-title":"Am J Transl Res"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.22888"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2010.03.008"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rbmo.2014.11.005"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.5478"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2021.102258"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dey336"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0040-1713429"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2010-0160"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2018-00242"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1177\/1933719114532841"},{"key":"e_1_2_8_48_1","volume-title":"PHYLIP (Phylogeny Inference Package) Version 3.6. Distributed by the Author","author":"Felsenstein J","year":"2015"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0503-2"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btw691"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-1199"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2013-14-10-r115"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-14-293"}],"container-title":["The Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.5778","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/path.5778","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.5778","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T11:20:29Z","timestamp":1761045629000},"score":1,"resource":{"primary":{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/10.1002\/path.5778"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,20]]},"references-count":52,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["10.1002\/path.5778"],"URL":"https:\/\/doi.org\/10.1002\/path.5778","archive":["Portico"],"relation":{},"ISSN":["0022-3417","1096-9896"],"issn-type":[{"value":"0022-3417","type":"print"},{"value":"1096-9896","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,20]]},"assertion":[{"value":"2020-12-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-08-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-09-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}