Genomic analysis defines clonal relationships of ductal carcinoma in situ and recurrent invasive breast cancer.
Authors
Sheinman, Michael
Fortunato, Angelo
Shah, Vandna
Sei, Emi
Xu, Mingchu
van den Belt-Dusebout, Alexandra W
Brugman, Wim
Casasent, Anna K
Davies, Helen R
Fu, Liping
Hardman, Timothy M
King, Lorraine M
Krete, Marielle
Kristel, Petra
de Maaker, Michiel
Marks, Jeffrey R
Mulder, Lennart
Nieboer, Frank
Nowinski, Salpie
Quist, Jelmar
Salinas-Souza, Carolina
Schaapveld, Michael
Schmidt, Marjanka K
Shami, Rana
Sridharan, Mathini
Zhang, John
Stobart, Hilary
Hwang, E Shelley
Grand Challenge PRECISION consortium
Thompson, Alastair M
Publication Date
2022-06Journal Title
Nat Genet
ISSN
1061-4036
Publisher
Springer Science and Business Media LLC
Volume
54
Issue
6
Pages
850-860
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Lips, E. H., Kumar, T., Megalios, A., Visser, L. L., Sheinman, M., Fortunato, A., Shah, V., et al. (2022). Genomic analysis defines clonal relationships of ductal carcinoma in situ and recurrent invasive breast cancer.. Nat Genet, 54 (6), 850-860. https://doi.org/10.1038/s41588-022-01082-3
Description
Funder: Career Development and Innovation Cancer Award, Guys & St Thomas’ Charity and the Cancer Research UK King’s Health Partners Centre at King’s College London.
Funder: T32 Translational Genomics Fellowship (NIH)
Funder: Single Cell Genomics CPRIT Core Facilities Grant (RP180684).
Abstract
Ductal carcinoma in situ (DCIS) is the most common form of preinvasive breast cancer and, despite treatment, a small fraction (5-10%) of DCIS patients develop subsequent invasive disease. A fundamental biologic question is whether the invasive disease arises from tumor cells in the initial DCIS or represents new unrelated disease. To address this question, we performed genomic analyses on the initial DCIS lesion and paired invasive recurrent tumors in 95 patients together with single-cell DNA sequencing in a subset of cases. Our data show that in 75% of cases the invasive recurrence was clonally related to the initial DCIS, suggesting that tumor cells were not eliminated during the initial treatment. Surprisingly, however, 18% were clonally unrelated to the DCIS, representing new independent lineages and 7% of cases were ambiguous. This knowledge is essential for accurate risk evaluation of DCIS, treatment de-escalation strategies and the identification of predictive biomarkers.
Keywords
Article, /631/67/1347, /631/208/514/1948, article
Sponsorship
Cancer Research UK (23916)
Identifiers
s41588-022-01082-3, 1082
External DOI: https://doi.org/10.1038/s41588-022-01082-3
This record's URL: https://www.repository.cam.ac.uk/handle/1810/338090
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
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