Cereser, B;
Jansen, M;
Austin, E;
Elia, G;
Mcfarlane, T;
van Deurzen, CH;
Sieuwerts, AM;
... Mcdonald, SA; + view all
(2018)
Analysis of clonal expansions through the normal and premalignant human breast epithelium reveals the presence of luminal stem cells.
Journal of Pathology
, 244
(1)
pp. 61-70.
10.1002/path.4989.
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Abstract
It is widely accepted that the cell of origin of breast cancer is the adult mammary epithelial stem cell; however, demonstrating the presence and location of tissue stem cells in the human breast has proved difficult. Furthermore, we do not know the clonal architecture of the normal and premalignant mammary epithelium or its cellular hierarchy. Here, we use deficiency in the mitochondrial enzyme cytochrome c oxidase (CCO), typically caused by somatic mutations in the mitochondrial genome, as a means to perform lineage tracing in the human mammary epithelium. PCR sequencing of laser-capture microdissected cells in combination with immunohistochemistry for markers of lineage differentiation was performed to determine the clonal nature of the mammary epithelium. We have shown that in the normal human breast, clonal expansions (defined here by areas of CCO deficiency) are typically uncommon and of limited size, but can occur at any site within the adult mammary epithelium. The presence of a stem cell population was shown by demonstrating multi-lineage differentiation within CCO-deficient areas. Interestingly, we observed infrequent CCO deficiency that was restricted to luminal cells, suggesting that niche succession, and by inference stem cell location, is located within the luminal layer. CCO-deficient areas appeared large within areas of ductal carcinoma in situ, suggesting that the rate of clonal expansion was altered in the premalignant lesion.
| Type: | Article |
|---|---|
| Title: | Analysis of clonal expansions through the normal and premalignant human breast epithelium reveals the presence of luminal stem cells |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/path.4989 |
| Publisher version: | http://dx.doi.org/10.1002/path.4989 |
| Language: | English |
| Additional information: | © 2017 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | Clonality; stem cells; mammary stem cell niche; ductal carcinoma in situ |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Pathology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10039738 |
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