High-depth whole genome sequencing of premalignant breast lesions reveals rearrangement hotspots and personalized management opportunities
Year: 2026
Type: article
Study design: Observational Study
Abstract: Ductal carcinoma in situ is a non-obligate precursor lesion of breast cancer. Often detected by mammography, most cases are managed through surgical and/or radiotherapy approaches. Today, it is not possible to predict which patients will progress to invasive disease. Here, we evaluate high-depth whole-genome sequenced ductal carcinoma in situ, enriched for high-grade clinical lesions, to understand whether deep WGS could reveal biological insights and/or personalized therapeutic vulnerabilities that may be targetable. We find genomic locations that are likely susceptible to producing the initiating lesion for structural variations prone to subsequent evolution, termed SHOREs. We additionally highlight individualized therapeutic potential that would otherwise not be appreciable without whole genome sequencing. We posit that holistic whole genome sequencing profiling could offer a more precise stratification approach, discerning higher-risk cases for prospective clinical studies on personalized therapies, from truly low-risk cases suitable for active monitoring.
Source: Nature Communications
Authors: Lucia Chmelova, Helen R. Davies, Andrea Degasperi, Giuseppe Rinaldi, Leon Wils, Daniella Black, Yasin Memari, Gene C. C. Koh, Scott Shooter, Lennart Mulder, Petra Kristel, Karoly Szuhai, Gino Prasad, Ivy Tsz-Lo Wong, Jens Luebeck, Yogesh Kumar, Jan Czarnecki, Shadi Basyuni, Zoya Kingsbury, Mark T. Ross, Øystein Garred, Margit Riis, Karin T. Lande, Johan Vallon-Christersson, Anna Ehinger, Amit Agrawal, Stuart A. McIntosh, Vineet Bafna, Paul S. Mischel, Fariba Behbod, Proteeti Bhattacharjee, Deborah Collyar, Helen Davies, Andrew Futreal, E. Shelley Hwang, Jos Jonkers, Esther H. Lips, Nicholas Navin, Serena Nik-Zainal, Donna Pinto, Daniel Rea, Elinor J. Sawyer, Marjanka Schmidt, Hilary Stobart, Alastair Thompson, Marja van Oirsouw, Jacco van Rheenen, Ellen Verschuur, Jelle Wesseling, Lodewyk F. A. Wessels, Jelle Wesseling, Johan Staaf, Therese Sørlie, Esther H. Lips, Serena Nik-Zainal
Institutions: University of Cambridge, The Netherlands Cancer Institute, Sunway University, Leiden University Medical Center, University of California San Diego, Stanford Medicine, Stanford University, Illumina (United Kingdom), Oslo University Hospital, Lund University, Medicon Village, Skåne University Hospital, Cambridge University Hospitals NHS Foundation Trust, Queen's University Belfast, University of Kansas, University of Kansas Medical Center, The University of Texas MD Anderson Cancer Center, Duke University, Duke Medical Center, Oncode Institute, University of Birmingham, King's College London, Baylor College of Medicine, Dan L Duncan Comprehensive Cancer Center, Borstkankervereniging Nederland, Delft University of Technology, University of Oslo
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: Breast Cancer Research Foundation, Cancer Research UK, National Institute for Health and Care Research, Department of Health and Social Care, Ministerie van Volksgezondheid, Welzijn en Sport, NIHR Cambridge Biomedical Research Centre, National Cancer Institute, National Institute of General Medical Sciences
Awards: G1152858438, G1357958584, G139696651, G1624442600, G1801247055, G2493601830, G2537968379, G2846829464, G350952706, G3584577881, G370598735, G4655236649, G506494406, G515689015, G5337071618, G6036597212, G6077662935, G6803452651, G7317995888, G7513802581, Selection of material and durability testing for a novel wearable surgical device (Splayer) for soft tissue surgery, Preventing Healthcare Associated Infection and Antimicrobial Resistance in Africa, G8687509801, Computational methods for detecting patterns of complex genomic variation
OpenAlex ID: W7161750474
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