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Recent studies of ovaries and Fallopian tubes in patients with\n \n BRCA1<\/jats:styled-content>\n <\/jats:italic>\n or\n \n BRCA2<\/jats:styled-content>\n <\/jats:italic>\n mutations have documented a pre\u2010metastatic intramucosal neoplasm that is found almost exclusively in the Fallopian tube, termed \u2018serous tubal intraepithelial carcinoma\u2019 or\n STIC<\/jats:styled-content>\n . Moreover, other proliferations, termed p53 signatures, secretory cell outgrowths (\n SCOUTs<\/jats:styled-content>\n ), and lower\u2010grade serous tubal intraepithelial neoplasms (\n STINs<\/jats:styled-content>\n ) fall short of\n STIC<\/jats:styled-content>\n but share similar alterations in expression, in keeping with an underpinning of genomic disturbances involved in, or occurring in parallel with, serous carcinogenesis. To gain insight into the cellular origins of this unique tubal pathway to high\u2010grade serous cancer, we cloned and both immortalized and transformed Fallopian tube stem cells (\n FTSCs<\/jats:styled-content>\n ). We demonstrated that pedigrees of\n FTSCs<\/jats:styled-content>\n were capable of multipotent differentiation and that the tumours derived from transformed\n FTSCs<\/jats:styled-content>\n shared the histological and molecular features of\n HGSC<\/jats:styled-content>\n . We also demonstrated that altered expression of some biomarkers seen in transformed\n FTSCs<\/jats:styled-content>\n and\n HGSCs<\/jats:styled-content>\n (stathmin,\n EZH2<\/jats:styled-content>\n ,\n CXCR4<\/jats:styled-content>\n ,\n CXCL12<\/jats:styled-content>\n , and\n FOXM1<\/jats:styled-content>\n ) could be seen as well in immortalized cells and their\n in vivo<\/jats:italic>\n counterparts\n SCOUTs<\/jats:styled-content>\n and\n STINs<\/jats:styled-content>\n . Thus, a whole\u2010genome transcriptome analysis comparing\n FTSCs<\/jats:styled-content>\n , immortalized\n FTSCs<\/jats:styled-content>\n , and transformed\n FTSCs<\/jats:styled-content>\n showed a clear molecular progression sequence that is recapitulated by the spectrum of accumulated perturbations characterizing the range of proliferations seen\n in vivo<\/jats:italic>\n . Biomarkers unique to\n STIC<\/jats:styled-content>\n relative to normal tubal epithelium provide a basis for novel detection approaches to early\n HGSC<\/jats:styled-content>\n , but must be viewed critically given their potential expression in lesser proliferations. Perturbations shared by both immortalized and transformed\n FTSCs<\/jats:styled-content>\n may provide unique early targets for prevention strategies. Central to these efforts has been the ability to clone and perpetuate multipotent\n FTSCs<\/jats:styled-content>\n . Copyright \u00a9 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.\n <\/jats:p>","DOI":"10.1002\/path.4649","type":"journal-article","created":{"date-parts":[[2015,9,28]],"date-time":"2015-09-28T08:36:46Z","timestamp":1443429406000},"page":"519-530","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":78,"title":["In vitro<\/i>\n and\n in vivo<\/i>\n correlates of physiological and neoplastic human Fallopian tube stem cells"],"prefix":"10.1002","volume":"238","author":[{"given":"Yusuke","family":"Yamamoto","sequence":"first","affiliation":[{"name":"The Jackson Laboratory for Genomic Medicine Farmington CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Ning","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory for Genomic Medicine Farmington CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brooke E","family":"Howitt","sequence":"additional","affiliation":[{"name":"Department of Pathology Brigham and Women's Hospital Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karishma","family":"Mehra","sequence":"additional","affiliation":[{"name":"Department of Pathology Brigham and Women's Hospital Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyan","family":"Wu","sequence":"additional","affiliation":[{"name":"Genome Institute of Singapore A\u2010STAR Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Wang","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory for Genomic Medicine Farmington CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Hong","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory for Genomic Medicine Farmington CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Kern","sequence":"additional","affiliation":[{"name":"Genome Institute of Singapore A\u2010STAR Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tay Seok","family":"Wei","sequence":"additional","affiliation":[{"name":"Genome Institute of Singapore A\u2010STAR Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Zhang","sequence":"additional","affiliation":[{"name":"Genome Institute of Singapore A\u2010STAR Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niranjan","family":"Nagarajan","sequence":"additional","affiliation":[{"name":"Genome Institute of Singapore A\u2010STAR Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debargha","family":"Basuli","sequence":"additional","affiliation":[{"name":"Departments of Molecular, Microbial and Structural Biology University of Connecticut Health Center Farmington CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzy","family":"Torti","sequence":"additional","affiliation":[{"name":"Departments of Molecular, Microbial and Structural Biology University of Connecticut Health Center Farmington CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Molly","family":"Brewer","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University of Connecticut Health Center Farmington CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahesh","family":"Choolani","sequence":"additional","affiliation":[{"name":"Division of Obstetrics and Gynecology National University of Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"McKeon","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory for Genomic Medicine Farmington CT USA"},{"name":"Genome Institute of Singapore A\u2010STAR Singapore"},{"name":"MultiClonal 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