Journal ArticleDOI
Aberrant luminal progenitors as the candidate target population for basal tumor development in BRCA1 mutation carriers
Elgene Lim,Elgene Lim,François Vaillant,Di Wu,Di Wu,Natasha C. Forrest,Bhupinder Pal,Adam H. Hart,Marie Liesse Asselin-Labat,David E. Gyorki,David E. Gyorki,Teresa Ward,Audrey Partanen,Frank Feleppa,Lily I. Huschtscha,Heather Thorne,Stephen B. Fox,Max Yan,Juliet D. French,Melissa A. Brown,Gordon K. Smyth,Jane E. Visvader,Geoffrey J. Lindeman,Geoffrey J. Lindeman,Geoffrey J. Lindeman +24 more
TLDR
It is found that breast tissue from BRCA1 mutation carriers harbors an expanded luminal progenitor population that shows factor-independent growth in vitro, and the findings suggest that an aberrant luminalprogenitor population is a target for transformation in BRCa1-associated basal tumors.Abstract:
Basal-like breast cancers arising in women carrying mutations in the BRCA1 gene, encoding the tumor suppressor protein BRCA1, are thought to develop from the mammary stem cell. To explore early cellular changes that occur in BRCA1 mutation carriers, we have prospectively isolated distinct epithelial subpopulations from normal mammary tissue and preneoplastic specimens from individuals heterozygous for a BRCA1 mutation. We describe three epithelial subsets including basal stem/progenitor, luminal progenitor and mature luminal cells. Unexpectedly, we found that breast tissue from BRCA1 mutation carriers harbors an expanded luminal progenitor population that shows factor-independent growth in vitro. Moreover, gene expression profiling revealed that breast tissue heterozygous for a BRCA1 mutation and basal breast tumors were more similar to normal luminal progenitor cells than any other subset, including the stem cell-enriched population. The c-KIT tyrosine kinase receptor (encoded by KIT) emerged as a key marker of luminal progenitor cells and was more highly expressed in BRCA1-associated preneoplastic tissue and tumors. Our findings suggest that an aberrant luminal progenitor population is a target for transformation in BRCA1-associated basal tumors .read more
Citations
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limma powers differential expression analyses for RNA-sequencing and microarray studies
Matthew E. Ritchie,Belinda Phipson,Di Wu,Yifang Hu,Charity W. Law,Wei Shi,Gordon K. Smyth,Gordon K. Smyth +7 more
TL;DR: The philosophy and design of the limma package is reviewed, summarizing both new and historical features, with an emphasis on recent enhancements and features that have not been previously described.
Journal ArticleDOI
A Perspective on Cancer Cell Metastasis
TL;DR: It is suggested that metastasis can be portrayed as a two-phase process: the first phase involves the physical translocation of a cancer cell to a distant organ, whereas the second encompasses the ability of the cancer cellto develop into a metastatic lesion at that distant site.
Journal ArticleDOI
Triple-negative breast cancer.
TL;DR: Triple-negative breast cancer, so called because it lacks expression of the estrogen receptor, progesterone receptor, and HER2, is often, but not always, a basal-like breast cancer.
Journal ArticleDOI
EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer
TL;DR: This review will provide potential mechanistic explanations for the association between EMT induction and the emergence of CSCs, and highlight recent studies implicating the function of TGF-β-regulated noncoding RNAs in driving EMT and promoting CSC self-renewal.
Journal ArticleDOI
Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer
Aleix Prat,Joel S. Parker,Olga Karginova,Cheng Fan,Chad A. Livasy,Jason I. Herschkowitz,Xiaping He,Charles M. Perou +7 more
TL;DR: It is confirmed that a prognostically relevant differentiation hierarchy exists across all breast cancers in which the claudin-low subtype most closely resembles the mammary epithelial stem cell.
References
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Linear Models and Empirical Bayes Methods for Assessing Differential Expression in Microarray Experiments
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Journal ArticleDOI
ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome.
Christophe Ginestier,Min Hee Hur,Emmanuelle Charafe-Jauffret,Florence Monville,Julie Dutcher,Marty Brown,Jocelyne Jacquemier,Patrice Viens,Celina G. Kleer,Suling Liu,Anne F. Schott,Daniel F. Hayes,Daniel Birnbaum,Max S. Wicha,Gabriela Dontu +14 more
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Immunohistochemical and Clinical Characterization of the Basal-Like Subtype of Invasive Breast Carcinoma
Torsten O. Nielsen,Forrest D. Hsu,Kristin C. Jensen,Maggie C.U. Cheang,Gamze Karaca,Zhiyuan Hu,Tina Hernandez-Boussard,Chad A. Livasy,Dave Cowan,Lynn G. Dressler,Lars A. Akslen,Joseph Ragaz,Allen M. Gown,C. Blake Gilks,Matt van de Rijn,Charles M. Perou +15 more
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Charles M. Perou,Therese Sørlie,Michael B. Eisen,Matt van de Rijn,Stefanie S. Jeffrey,Christian A. Rees,Jonathan R. Pollack,Douglas T. Ross,Hilde Johnsen,Lars A. Akslen,Øystein Fluge,Alexander Pergamenschikov,Cheryl A. Williams,Shirley Zhu,Per Eystein Lønning,Anne Lise Børresen-Dale,Patrick O. Brown,David Botstein +17 more