Ethnicity-dependent and -independent heterogeneity in healthy normal breast hierarchy impacts tumor characterization

dc.contributor.authorNakshatri, Harikrishna
dc.contributor.authorAnjanappa, Manjushree
dc.contributor.authorBhat-Nakshatri, Poornima
dc.contributor.departmentDepartment of Surgery, IU School of Medicineen_US
dc.date.accessioned2016-02-26T15:18:57Z
dc.date.available2016-02-26T15:18:57Z
dc.date.issued2015-08-27
dc.description.abstractRecent reports of widespread genetic variation affecting regulation of gene expression raise the possibility of significant inter-individual differences in stem-progenitor-mature cell hierarchy in adult organs. This has not been explored because of paucity of methods to quantitatively assess subpopulation of normal epithelial cells on individual basis. We report the remarkable inter-individual differences in differentiation capabilities as documented by phenotypic heterogeneity in stem-progenitor-mature cell hierarchy of the normal breast. Ethnicity and genetic predisposition are partly responsible for this heterogeneity, evidenced by the finding that CD44+/CD24- and PROCR+/EpCAM- multi-potent stem cells were elevated significantly in African American women compared with Caucasians. ALDEFLUOR+ luminal stem/progenitor cells were lower in BRCA1-mutation carriers compared with cells from healthy donors (p = 0.0014). Moreover, tumor and adjoining-normal breast cells of the same patients showed distinct CD49f+/EpCAM+ progenitor, CD271+/EpCAM- basal, and ALDEFLUOR+ cell profiles. These inter-individual differences in the rate of differentiation in the normal breast may contribute to a substantial proportion of transcriptome, epigenome, and signaling pathway alterations and consequently has the potential to spuriously magnify the extent of documented tumor-specific gene expression. Therefore, comparative analysis of phenotypically defined subpopulations of normal and tumor cells on an individual basis may be required to identify cancer-specific aberrations.en_US
dc.identifier.citationNakshatri, H., Anjanappa, M., & Bhat-Nakshatri, P. (2015). Ethnicity-Dependent and -Independent Heterogeneity in Healthy Normal Breast Hierarchy Impacts Tumor Characterization. Scientific Reports, 5, 13526. http://doi.org/10.1038/srep13526en_US
dc.identifier.urihttps://hdl.handle.net/1805/8519
dc.language.isoen_USen_US
dc.publisherNature Publishing Groupen_US
dc.relation.isversionof10.1038/srep13526en_US
dc.relation.journalScientific Reportsen_US
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/us/
dc.sourcePMCen_US
dc.subjectGene expressionen_US
dc.subjectStem-progenitor-mature cell hierarchyen_US
dc.subjectBreasten_US
dc.subjectLuminal stem/progenitor cellsen_US
dc.subjectTumor cellsen_US
dc.titleEthnicity-dependent and -independent heterogeneity in healthy normal breast hierarchy impacts tumor characterizationen_US
dc.typeArticleen_US
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