Please use this identifier to cite or link to this item: http://docs.prosentient.com.au/prosentientjspui/handle/1/11085
Title: Atypical ductal hyperplasia is a multipotent precursor of breast carcinoma.
Authors: Kader, Tanjina
Hill, Prue
Zethoven, Magnus
Goode, David L
Elder, Kenneth
Thio, Niko
Doyle, Maria
Semple, Timothy
Sufyan, Wajiha
Byrne, David J
Pang, Jia-Min B
Murugasu, Anand
Miligy, Islam M
Green, Andrew R
Rakha, Emad A
Fox, Stephen B
Mann, G Bruce
Campbell, Ian G
Gorringe, Kylie L
Affiliation: Peter MacCallum Cancer Centre, 305 Grattan St, Melbourne, Australia, 3000.. The Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia, 3010..
Department of Anatomical Pathology, St Vincent's Hospital, Fitzroy, Australia..
Peter MacCallum Cancer Centre, 305 Grattan St, Melbourne, Australia, 3000..
Peter MacCallum Cancer Centre, 305 Grattan St, Melbourne, Australia, 3000.. The Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia, 3010..
The Breast Service, The Royal Women's Hospital, Melbourne, Australia..
Peter MacCallum Cancer Centre, 305 Grattan St, Melbourne, Australia, 3000..
Peter MacCallum Cancer Centre, 305 Grattan St, Melbourne, Australia, 3000..
Peter MacCallum Cancer Centre, 305 Grattan St, Melbourne, Australia, 3000..
Territory Pathology, Royal Darwin Hospital, Darwin, NT..
Peter MacCallum Cancer Centre, 305 Grattan St, Melbourne, Australia, 3000..
Peter MacCallum Cancer Centre, 305 Grattan St, Melbourne, Australia, 3000..
The Breast Service, The Royal Women's Hospital, Melbourne, Australia..
Nottingham Breast Cancer Research Centre, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham and Department of Histopathology, Nottingham University Hospitals NHS Trust, City Hospital, Nottingham, UK..
Nottingham Breast Cancer Research Centre, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham and Department of Histopathology, Nottingham University Hospitals NHS Trust, City Hospital, Nottingham, UK..
Nottingham Breast Cancer Research Centre, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham and Department of Histopathology, Nottingham University Hospitals NHS Trust, City Hospital, Nottingham, UK..
Peter MacCallum Cancer Centre, 305 Grattan St, Melbourne, Australia, 3000..
The Breast Service, The Royal Women's Hospital, Melbourne, Australia..
Peter MacCallum Cancer Centre, 305 Grattan St, Melbourne, Australia, 3000.. The Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia, 3010.. Department of Clinical Pathology, The University of Melbourne, Parkville, Australia, 3010..
Peter MacCallum Cancer Centre, 305 Grattan St, Melbourne, Australia, 3000.. The Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia, 3010.. Department of Clinical Pathology, The University of Melbourne, Parkville, Australia, 3010..
Issue Date: 6-Mar-2019
Citation: The Journal of pathology 2019-03-06
Abstract: The current model for breast cancer progression proposes independent "low-grade (LG) like" and "high-grade (HG) like" pathways but lacks a known precursor to HG cancer. We applied low coverage whole genome sequencing to atypical ductal hyperplasia (ADH) with and without carcinoma to shed light on breast cancer progression. 14/20 isolated ADH cases harboured at least one copy number alteration (CNA), but had fewer aberrations than LG or HG ductal carcinoma in situ (DCIS). ADH carried more HG-like CNA than LG DCIS (eg. 8q gain). Correspondingly, 64% (7/11) of ADH cases with synchronous HG carcinoma were clonally related, similar to LG carcinoma (67%, 6/9). This study represents a significant shift in our understanding of breast cancer progression, with ADH as a common precursor lesion to the independent "low-grade like" and "high-grade like" pathways. These data suggest that ADH can be a precursor of HG breast cancer and that LG and HG carcinomas can evolve from a similar ancestor lesion. We propose that although LG DCIS may be committed to a LG molecular pathway, ADH may remain multipotent, progressing to either LG or HG carcinoma. This multipotent nature suggests that some ADH could be more clinically significant than LG DCIS, requiring biomarkers for personalising management.
URI: http://docs.prosentient.com.au/prosentientjspui/handle/1/11085
DOI: 10.1002/path.5262
ORCID: https://orcid.org/0000-0002-1463-7593
https://orcid.org/0000-0002-0488-5913
https://orcid.org/0000-0002-7773-4155
Type: Journal Article
Subjects: atypical ductal hyperplasia
benign breast disease
breast cancer progression
clonal
copy number
ductal carcinoma in situ
pre-malignant breast lesions
whole genome sequencing
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