{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T18:53:03Z","timestamp":1793040783375,"version":"4.5.0"},"reference-count":85,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T00:00:00Z","timestamp":1616371200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP19K09822"],"award-info":[{"award-number":["JP19K09822"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Numerous epidemiological and histopathological studies support the notion that clear cell and endometrioid carcinomas derive from ovarian endometriosis. Accordingly, these histologic types are referred to as \u201cendometriosis-associated ovarian cancer\u201d (EAOC). Although the uterine endometrium is also considered an origin of endometriosis, the molecular mechanism involved in transformation of the uterine endometrium to EAOC via ovarian endometriosis has not yet been clarified. Recent studies based on high-throughput sequencing technology have revealed that cancer-associated gene mutations frequently identified in EAOC may exist in the normal uterine endometrial epithelium and ovarian endometriotic epithelium. The continuum of genomic alterations from the uterine endometrium to endometriosis and EAOC has been described, though the significance of cancer-associated gene mutations in the uterine endometrium or endometriosis remains unclear. In this review, we summarize current knowledge regarding the molecular characteristics of the uterine endometrium, endometriosis, and EAOC and discuss the molecular mechanism of cancer development from the normal endometrium through endometriosis in an effort to prevent EAOC.<\/jats:p>","DOI":"10.3390\/cancers13061439","type":"journal-article","created":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T11:13:26Z","timestamp":1616411606000},"page":"1439","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["How Does Endometriosis Lead to Ovarian Cancer? The Molecular Mechanism of Endometriosis-Associated Ovarian Cancer Development"],"prefix":"10.3390","volume":"13","author":[{"given":"Nozomi","family":"Yachida","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2254-3378","authenticated-orcid":false,"given":"Kosuke","family":"Yoshihara","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manako","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuaki","family":"Suda","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9673-7941","authenticated-orcid":false,"given":"Ryo","family":"Tamura","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Enomoto","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.ajpath.2020.09.006","article-title":"The Origin of Ovarian Cancer Species and Precancerous Landscape","volume":"191","author":"Shih","year":"2021","journal-title":"Am. J. Pathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.ygyno.2011.06.017","article-title":"The association between endometriosis and gynecological cancers and breast cancer: A review of epidemiological data","volume":"123","author":"Munksgaard","year":"2011","journal-title":"Gynecol. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/S1470-2045(11)70404-1","article-title":"Association between endometriosis and risk of histological subtypes of ovarian cancer: A pooled analysis of case\u2013control studies","volume":"13","author":"Pearce","year":"2012","journal-title":"Lancet Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1002\/ijc.21845","article-title":"Molecular genetic evidence that endometriosis is a precursor of ovarian cancer","volume":"119","author":"Prowse","year":"2006","journal-title":"Int. J. Cancer."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1002\/path.2940","article-title":"PIK3CA mutation is an early event in the development of endometriosis-associated ovarian clear cell adenocarcinoma","volume":"225","author":"Yamamoto","year":"2011","journal-title":"J. Pathol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1056\/NEJMoa1008433","article-title":"ARID1A mutations in endometriosis-associated ovarian carcinomas","volume":"363","author":"Wiegand","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bpobgyn.2018.06.001","article-title":"Risk for and consequences of endometriosis: A critical epidemiologic review","volume":"51","author":"Shafrir","year":"2018","journal-title":"Best Pract. Res. Clin. Obstet. Gynaecol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1093\/humrep\/dex057","article-title":"Measuring health-related quality of life in women with endometriosis: Comparing the clinimetric properties of the Endometriosis Health Profile-5 (EHP-5) and the EuroQol-5D (EQ-5D)","volume":"32","author":"Aubry","year":"2017","journal-title":"Hum. Reprod."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1146\/annurev-pathmechdis-012419-032654","article-title":"The Origin and Pathogenesis of Endometriosis","volume":"15","author":"Wang","year":"2020","journal-title":"Annu Rev. Pathol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/S0002-9378(15)30003-X","article-title":"Peritoneal endometriosis due to the menstrual dissemination of endometrial tissue into the peritoneal cavity","volume":"14","author":"Sampson","year":"1927","journal-title":"Am. J. Obstet Gynecol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1159\/000052855","article-title":"Coelomic metaplasia theory of endometriosis: Evidence from in vivo studies and an in vitro experimental model","volume":"47","author":"Matsuura","year":"1999","journal-title":"Gynecol. Obstet. Investig."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1016\/j.celrep.2018.07.037","article-title":"Clonal Expansion and Diversification of Cancer-Associated Mutations in Endometriosis and Normal Endometrium","volume":"24","author":"Suda","year":"2018","journal-title":"Cell Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1056\/NEJMoa1614814","article-title":"Cancer-Associated Mutations in Endometriosis without Cancer","volume":"376","author":"Anglesio","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1093\/humrep\/dey332","article-title":"Iatrogenic endometriosis harbors somatic cancer-driver mutations","volume":"34","author":"Lac","year":"2019","journal-title":"Hum. Reprod."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1038\/ng.3849","article-title":"Genomic consequences of aberrant DNA repair mechanisms stratify ovarian cancer histotypes","volume":"49","author":"Wang","year":"2017","journal-title":"Nat. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1038\/bjc.2017.228","article-title":"Whole-genome sequencing revealed novel prognostic biomarkers and promising targets for therapy of ovarian clear cell carcinoma","volume":"117","author":"Itamochi","year":"2017","journal-title":"Br. J. Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2246","DOI":"10.1016\/j.ajpath.2017.06.012","article-title":"Exome Sequencing Landscape Analysis in Ovarian Clear Cell Carcinoma Shed Light on Key Chromosomal Regions and Mutation Gene Networks","volume":"187","author":"Murakami","year":"2017","journal-title":"Am. J. Pathol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1002\/gcc.22507","article-title":"Identification of somatic genetic alterations in ovarian clear cell carcinoma with next generation sequencing","volume":"57","author":"Shibuya","year":"2018","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.ygyno.2017.12.005","article-title":"Genomic landscape of ovarian clear cell carcinoma via whole exome sequencing","volume":"148","author":"Kim","year":"2018","journal-title":"Gynecol. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.ygyno.2019.07.012","article-title":"Molecular profiling and molecular classification of endometrioid ovarian carcinomas","volume":"154","author":"Cybulska","year":"2019","journal-title":"Gynecol. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.ygyno.2020.02.011","article-title":"An integrated molecular profile of endometrioid ovarian cancer","volume":"157","author":"Pierson","year":"2020","journal-title":"Gynecol. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4995","DOI":"10.1038\/s41467-020-18819-5","article-title":"Molecular stratification of endometrioid ovarian carcinoma predicts clinical outcome","volume":"11","author":"Hollis","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1126\/science.277.5325.567","article-title":"Dual role of phosphatidylinositol-3,4,5-trisphosphate in the activation of protein kinase B","volume":"277","author":"Stokoe","year":"1997","journal-title":"Science"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.ygyno.2005.09.047","article-title":"PTEN expression in clear cell adenocarcinoma of the ovary","volume":"101","author":"Hashiguchi","year":"2006","journal-title":"Gynecol. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1038\/modpathol.2013.216","article-title":"Loss of ARID1A expression and its relationship with PI3K-Akt pathway alterations and ZNF217 amplification in ovarian clear cell carcinoma","volume":"27","author":"Huang","year":"2014","journal-title":"Mod. Pathol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1038\/s41416-020-0900-0","article-title":"Clinical and pathological associations of PTEN expression in ovarian cancer: A multicentre study from the Ovarian Tumour Tissue Analysis Consortium","volume":"123","author":"Martins","year":"2020","journal-title":"Br. J. Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1111\/his.12543","article-title":"Ovarian and endometrial endometrioid adenocarcinomas have distinct profiles of microsatellite instability, PTEN expression, and ARID1A expression","volume":"66","author":"Huang","year":"2015","journal-title":"Histopathology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s00428-011-1169-8","article-title":"PIK3CA mutations and loss of ARID1A protein expression are early events in the development of cystic ovarian clear cell adenocarcinoma","volume":"460","author":"Yamamoto","year":"2012","journal-title":"Virchows Arch."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Iida, Y., Okamoto, A., Hollis, R.L., Gourley, C., and Herrington, C.S. (2020). Clear cell carcinoma of the ovary: A clinical and molecular perspective. Int. J. Gynecol. Cancer.","DOI":"10.1136\/ijgc-2020-001656"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"5404","DOI":"10.1158\/1078-0432.CCR-09-0365","article-title":"mTOR is a promising therapeutic target both in cisplatin-sensitive and cisplatin-resistant clear cell carcinoma of the ovary","volume":"15","author":"Mabuchi","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e31","DOI":"10.3802\/jgo.2016.27.e31","article-title":"Clear cell carcinoma of the ovary: Molecular insights and future therapeutic perspectives","volume":"27","author":"Mabuchi","year":"2016","journal-title":"J. Gynecol. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2547","DOI":"10.1038\/onc.2015.329","article-title":"Stamping out RAF and MEK1\/2 to inhibit the ERK1\/2 pathway: An emerging threat to anticancer therapy","volume":"35","author":"Mandal","year":"2016","journal-title":"Oncogene"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"17808","DOI":"10.1038\/s41598-019-54116-y","article-title":"Germline and somatic mutations of homologous recombination-associated genes in Japanese ovarian cancer patients","volume":"9","author":"Sugino","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1146\/annurev.biochem.052308.093131","article-title":"The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway","volume":"79","author":"Lieber","year":"2010","journal-title":"Annu. Rev. Biochem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4578","DOI":"10.1182\/blood-2010-01-265769","article-title":"The PARP inhibitor olaparib induces significant killing of ATM-deficient lymphoid tumor cells in vitro and in vivo","volume":"116","author":"Weston","year":"2010","journal-title":"Blood"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.1056\/NEJMoa1911440","article-title":"Olaparib for Metastatic Castration-Resistant Prostate Cancer","volume":"382","author":"Mateo","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1038\/ng.2760","article-title":"Pan-cancer patterns of somatic copy number alteration","volume":"45","author":"Zack","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1997","DOI":"10.1158\/1078-0432.CCR-09-2105","article-title":"DNA copy numbers profiles in affinity-purified ovarian clear cell carcinoma","volume":"16","author":"Kuo","year":"2010","journal-title":"Clin. Cancer Res."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Uehara, Y., Oda, K., Ikeda, Y., Koso, T., Tsuji, S., Yamamoto, S., Asada, K., Sone, K., Kurikawa, R., and Makii, C. (2015). Integrated copy number and expression analysis identifies profiles of whole-arm chromosomal alterations and subgroups with favorable outcome in ovarian clear cell carcinomas. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0132751"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2846","DOI":"10.1002\/cncr.26598","article-title":"Prognostic and therapeutic impact of the chromosome 20q13.2 ZNF217 locus amplification in ovarian clear cell carcinoma","volume":"118","author":"Rahman","year":"2012","journal-title":"Cancer"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Okamoto, A., Sehouli, J., Yanaihara, N., Hirata, Y., Braicu, I., Kim, B.G., Takakura, S., Saito, M., Yanagida, S., and Takenaka, M. (2015). Somatic copy number alterations associated with Japanese or endometriosis in ovarian clear cell adenocarcinoma. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0116977"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Yamashita, Y., Akatsuka, S., Shinjo, K., Yatabe, Y., Kobayashi, H., Seko, H., Kajiyama, H., Kikkawa, F., Takahashi, T., and Toyokuni, S. (2013). Met is the most frequently amplified gene in endometriosis-associated ovarian clear cell adenocarcinoma and correlates with worsened prognosis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0057724"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.ygyno.2018.09.001","article-title":"Genomics to immunotherapy of ovarian clear cell carcinoma: Unique opportunities for management","volume":"151","author":"Oda","year":"2018","journal-title":"Gynecol. Oncol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1097\/PAS.0000000000000550","article-title":"Morphological and Immunohistochemical Reevaluation of Tumors Initially Diagnosed as Ovarian Endometrioid Carcinoma with Emphasis on High-grade Tumors","volume":"40","author":"Lim","year":"2016","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"The Cancer Genome Atlas Research Network, Kandoth, C., Schultz, N., Cherniack, A.D., Akbani, R., Liu, Y., Shen, H., Robertson, A.G., Pashtan, I., and Shen, R. (2013). Integrated genomic characterization of endometrial carcinoma. Nature, 497, 67\u201373.","DOI":"10.1038\/nature12113"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1097\/PAS.0000000000001016","article-title":"High-grade Endometrioid Carcinoma of the Ovary: A Clinicopathologic Study of 30 Cases","volume":"42","author":"Assem","year":"2018","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1748","DOI":"10.1038\/modpathol.2017.81","article-title":"Molecular-based classification algorithm for endometrial carcinoma categorizes ovarian endometrioid carcinoma into prognostically significant groups","volume":"30","author":"Xu","year":"2017","journal-title":"Mod. Pathol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1056\/NEJMra0907178","article-title":"Genomics and the continuum of cancer care","volume":"364","author":"McDermott","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1038\/nrc3066","article-title":"Cell-free nucleic acids as biomarkers in cancer patients","volume":"11","author":"Schwarzenbach","year":"2011","journal-title":"Nat. Rev. Cancer"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Noguchi, T., Iwahashi, N., Sakai, K., Matsuda, K., Matsukawa, H., Toujima, S., Nishio, K., and Ino, K. (2020). Comprehensive Gene Mutation Profiling of Circulating Tumor DNA in Ovarian Cancer: Its Pathological and Prognostic Impact. Cancers, 12.","DOI":"10.3390\/cancers12113382"},{"key":"ref_51","first-page":"7052","article-title":"Loss of heterozygosity on 10q23.3 and mutation of the tumor suppressor gene PTEN in benign endometrial cyst of the ovary: Possible sequence progression from benign endometrial cyst to endometrioid carcinoma and clear cell carcinoma of the ovary","volume":"60","author":"Sato","year":"2000","journal-title":"Cancer Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1038\/modpathol.2011.189","article-title":"Loss of ARID1A protein expression occurs as an early event in ovarian clear-cell carcinoma development and frequently coexists with PIK3CA mutations","volume":"25","author":"Yamamoto","year":"2011","journal-title":"Mod. Pathol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"14260","DOI":"10.1038\/s41598-020-71273-7","article-title":"ARID1A protein expression is retained in ovarian endometriosis with ARID1A loss-of-function mutations: Implication for the two-hit hypothesis","volume":"10","author":"Yachida","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s10147-019-01536-5","article-title":"Endometriosis-associated ovarian cancer occurs early during follow-up of endometrial cysts","volume":"25","author":"Murakami","year":"2020","journal-title":"Int. J. Clin. Oncol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/nrc2772","article-title":"Senescence in tumours: Evidence from mice and humans","volume":"10","author":"Collado","year":"2010","journal-title":"Nat. Rev. Cancer"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"78263","DOI":"10.18632\/oncotarget.21051","article-title":"Endometriosis: Benign, malignant, or something in between?","volume":"8","author":"Chui","year":"2017","journal-title":"Oncotarget"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1080\/09513590802366204","article-title":"The role of iron in the pathogenesis of endometriosis","volume":"25","author":"Kobayashi","year":"2009","journal-title":"Gynecol. Endocrinol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"20678","DOI":"10.1038\/s41598-020-77666-y","article-title":"Differences in gynecologic tumor development in Amhr2-Cre mice with KRAS(G12D) or KRAS(G12V) mutations","volume":"10","author":"Kun","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1038\/s41467-020-15497-1","article-title":"Oncogenic Kras(G12D) causes myeloproliferation via NLRP3 inflammasome activation","volume":"11","author":"Hamarsheh","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.ccr.2011.12.006","article-title":"KrasG12D-induced IKK2\/beta\/NF-kappaB activation by IL-1alpha and p62 feedforward loops is required for development of pancreatic ductal adenocarcinoma","volume":"21","author":"Ling","year":"2012","journal-title":"Cancer Cell"},{"key":"ref_61","first-page":"4311","article-title":"Molecular identification of latent precancers in histologically normal endometrium","volume":"61","author":"Mutter","year":"2001","journal-title":"Cancer Res."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Risques, R.A., and Kennedy, S.R. (2018). Aging and the rise of somatic cancer-associated mutations in normal tissues. PLoS Genet., 14.","DOI":"10.1371\/journal.pgen.1007108"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.ccell.2020.11.002","article-title":"Normal Somatic Mutations in Cancer Transformation","volume":"39","author":"Wijewardhane","year":"2021","journal-title":"Cancer Cell."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1126\/science.aaa6806","article-title":"Tumor evolution. High burden and pervasive positive selection of somatic mutations in normal human skin","volume":"348","author":"Martincorena","year":"2015","journal-title":"Science"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1038\/s41586-018-0811-x","article-title":"Age-related remodelling of oesophageal epithelia by mutated cancer drivers","volume":"565","author":"Yokoyama","year":"2019","journal-title":"Nature"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1038\/s41586-019-1672-7","article-title":"The landscape of somatic mutation in normal colorectal epithelial cells","volume":"574","author":"Olafsson","year":"2019","journal-title":"Nature"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/j.cell.2019.03.026","article-title":"Somatic Mutations Increase Hepatic Clonal Fitness and Regeneration in Chronic Liver Disease","volume":"177","author":"Zhu","year":"2019","journal-title":"Cell"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1126\/science.aba8347","article-title":"Extensive heterogeneity in somatic mutation and selection in the human bladder","volume":"370","author":"Lawson","year":"2020","journal-title":"Science"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1038\/s41586-020-2214-z","article-title":"The mutational landscape of normal human endometrial epithelium","volume":"580","author":"Moore","year":"2020","journal-title":"Nature"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1002\/path.5314","article-title":"Oncogenic mutations in histologically normal endometrium: The new normal?","volume":"249","author":"Lac","year":"2019","journal-title":"J. Pathol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1097\/IGC.0b013e31826b5dcc","article-title":"Loss of ARID1A expression is an early molecular event in tumor progression from ovarian endometriotic cyst to clear cell and endometrioid carcinoma","volume":"22","author":"Ayhan","year":"2012","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.ijgo.2015.02.021","article-title":"The ARID1A pathway in ovarian clear cell and endometrioid carcinoma, contiguous endometriosis, and benign endometriosis","volume":"130","author":"Chene","year":"2015","journal-title":"Int. J. Gynaecol. Obstet."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1097\/IGC.0000000000000698","article-title":"BAF250a Expression in Atypical Endometriosis and Endometriosis-Associated Ovarian Cancer","volume":"26","author":"Stamp","year":"2016","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1002\/path.4516","article-title":"Multifocal endometriotic lesions associated with cancer are clonal and carry a high mutation burden","volume":"236","author":"Anglesio","year":"2015","journal-title":"J. Pathol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"607","DOI":"10.3892\/or.2015.4421","article-title":"ARID1A gene mutation in ovarian and endometrial cancers (Review)","volume":"35","author":"Takeda","year":"2016","journal-title":"Oncol. Rep."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2120","DOI":"10.1101\/gr.137596.112","article-title":"Whole-exome sequencing combined with functional genomics reveals novel candidate driver cancer genes in endometrial cancer","volume":"22","author":"Liang","year":"2012","journal-title":"Genome Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"6118","DOI":"10.1038\/ncomms7118","article-title":"Coexistent ARID1A\u2013PIK3CA mutations promote ovarian clear-cell tumorigenesis through pro-tumorigenic inflammatory cytokine signalling","volume":"6","author":"Chandler","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"3554","DOI":"10.1038\/s41467-019-11403-6","article-title":"ARID1A and PI3-kinase pathway mutations in the endometrium drive epithelial transdifferentiation and collective invasion","volume":"10","author":"Wilson","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1038\/436642a","article-title":"Tumour biology: Senescence in premalignant tumours","volume":"436","author":"Collado","year":"2005","journal-title":"Nature"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Yachida, N., Yoshihara, K., Suda, K., Nakaoka, H., Ueda, H., Sugino, K., Yamaguchi, M., Mori, Y., Yamawaki, K., and Tamura, R. (2021). Biological significance of KRAS mutant allele expression in ovarian endometriosis. Cancer Sci.","DOI":"10.1111\/cas.14871"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.1056\/NEJMp1508811","article-title":"The Path to Cancer\u2014Three Strikes and You\u2019re Out","volume":"373","author":"Vogelstein","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"De Palma, F.D.E., D\u2019Argenio, V., Pol, J., Kroemer, G., Maiuri, M.C., and Salvatore, F. (2019). The Molecular Hallmarks of the Serrated Pathway in Colorectal Cancer. Cancers, 11.","DOI":"10.3390\/cancers11071017"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"3000","DOI":"10.1111\/cas.14507","article-title":"Clonal lineage from normal endometrium to ovarian clear cell carcinoma through ovarian endometriosis","volume":"111","author":"Suda","year":"2020","journal-title":"Cancer Sci."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1073\/pnas.68.4.820","article-title":"Mutation and cancer: Statistical study of retinoblastoma","volume":"68","author":"Knudson","year":"1971","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1126\/science.aax5525","article-title":"Mutated clones are the new normal","volume":"364","author":"Tomasetti","year":"2019","journal-title":"Science"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/6\/1439\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:39:01Z","timestamp":1760161141000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/6\/1439"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,22]]},"references-count":85,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["cancers13061439"],"URL":"https:\/\/doi.org\/10.3390\/cancers13061439","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,22]]}}}