Journal article

Atypical ductal hyperplasia is a multipotent precursor of breast carcinoma

Tanjina Kader, Prue Hill, Magnus Zethoven, David L Goode, Kenneth Elder, Niko Thio, Maria Doyle, Timothy Semple, Wajiha Sufyan, David J Byrne, Jia-Min B Pang, Anand Murugasu, Islam M Miligy, Andrew R Green, Emad A Rakha, Stephen B Fox, G Bruce Mann, Ian G Campbell, Kylie L Gorringe



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. Fourteen out of twenty 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 (e.g. 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 represen..

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Awarded by Australian National Health and Medical Research Council

Funding Acknowledgements

We thank the Peter MacCallum Cancer Centre Bioinformatics and Molecular Genomics core facilities, which were supported by the Australian Cancer Research Foundation. We also thank A/P Ken Opeskin from the Department of Anatomical Pathology, St Vincent's Hospital for the assessment of lesions and Maria Bisignano from Melbourne Health Pathology Service for coordinating ADH cases. We thank the Nottingham Health Science Biobank and Breast Cancer Now Tissue Bank for the provision of tissue samples. This study was funded by the Australian National Health and Medical Research Council (APP1063092) and supported by the Peter MacCallum Cancer Foundation. TK was supported by a University of Melbourne International Research Scholarship. KLG was supported by a Victorian Cancer Agency Mid-Career Fellowship and a Union for International Cancer Control Yamagiwa Yoshida Memorial International Study Grant.