Atypical ductal hyperplasia is a multipotent precursor of breast carcinoma
Institution: Peter MacCallum Cancer Centre; University of Melbourne
Corresponding Researcher: Kylie Gorringe
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Summary
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 sequencingto 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 feweraberrations than LG or HG ductal carcinomain situ(DCIS). ADH carried more HG-like CNA than LG DCIS (e.g. 8qgain). Correspondingly, 64% (7/11) of ADH cases with synchronous HG carcinoma were clonally related, similar toLG 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. Thesedata suggest that ADH can be a precursor of HG breast cancer and that LG and HG carcinomas can evolve froma similar ancestor lesion. We propose that although LG DCIS may be committed to a LG molecular pathway, ADHmay remain multipotent, progressing to either LG or HG carcinoma. This multipotent nature suggests that someADH cases could be more clinically significant than LG DCIS, requiring biomarkers for personalising management.
