@article{f119751c09654c74989aea98e483ea0f,
title = "Genomic analysis defines clonal relationships of ductal carcinoma in situ and recurrent invasive breast cancer",
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.",
author = "{Grand Challenge PRECISION Consortium} and Lips, {Esther H.} and Tapsi Kumar and Anargyros Megalios and Visser, {Lindy L.} and Michael Sheinman and Angelo Fortunato and Vandna Shah and Marlous Hoogstraat and Emi Sei and Diego Mallo and Maria Roman-Escorza and Ahmed, {Ahmed A.} and Mingchu Xu and {van den Belt-Dusebout}, {Alexandra W.} and Wim Brugman and Casasent, {Anna K.} and Karen Clements and Davies, {Helen R.} and Liping Fu and Anita Grigoriadis and Hardman, {Timothy M.} and King, {Lorraine M.} and Marielle Krete and Petra Kristel and {de Maaker}, Michiel and Maley, {Carlo C.} and Marks, {Jeffrey R.} and Menegaz, {Brian A.} and Lennart Mulder and Frank Nieboer and Salpie Nowinski and Sarah Pinder and Jelmar Quist and Carolina Salinas-Souza and Michael Schaapveld and Schmidt, {Marjanka K.} and Shaaban, {Abeer M.} and Rana Shami and Mathini Sridharan and John Zhang and Hilary Stobart and Deborah Collyar and Serena Nik-Zainal and Wessels, {Lodewyk F.A.} and Hwang, {E. Shelley} and Navin, {Nicholas E.} and Futreal, {P. Andrew} and Futreal, {P. Andrew} and Hwang, {E. Shelley} and Sawyer, {Elinor J.}",
note = "Funding Information: Authors listed from ** to ***are in alphabetical order. WES sequencing support was provided by the Moon Shot Cancer Genomics Laboratory, X. Song and L.D. Little, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. We thank all patients in the US, The Netherlands and the UK who have donated their data and tissue for this work. We also wish to thank all the collaborating hospitals, and in particular, pathology departments, and all persons who have helped in the process of data collection and analysis. The authors thank the registration team of the Netherlands Comprehensive Cancer Organization (IKNL) for the collection of data for the Netherlands Cancer Registry. We thank PALGA, the nationwide network and registry of histo- and cytopathology in the Netherlands, for providing pathology data and for their help in the collection of the residual patient material. We acknowledge the staff of the NKI-AVL Core Facility Molecular Pathology and Biobanking for their technical support and the staff of the NKI-AVL Genomics Core Facility and Ronald van Marion of the Erasmus University Medical Center for their sequencing support. We thank T. Hardiman and R. Kataria for their input during development of the Breakclone method. The data for the Sloane Project is based on information collected and quality assured by the PHE Population Screening Programmes. Access to the data was facilitated by the PHE Office for Data Release. We are also grateful for T. Lynch, who helped to expertly coordinate the PRECISON team at Duke University. This work was supported by Cancer Research UK and KWF Kankerbestrijding (reference C38317/A24043) and Breast Cancer Now (2014NovTAP379) with support from Walk the Walk. E.J.S. is funded by a Career Development and Innovation Cancer Award, Guys and St Thomas{\textquoteright} Charity and the Cancer Research UK King{\textquoteright}s Health Partners Centre at King{\textquoteright}s College London. T.K. is funded by a T32 Translational Genomics Fellowship. This work was supported by grants to N.E.N. by the National Cancer Institute (RO1CA240526) and the CPRIT Single Cell Genomics Center (RP180684). E.S.H. is funded by RFA-CA-17-035 (NIH), 1505-30497 (PCORI), BCRF 19-074 (BCRF), DOD BC132057 and R01 CA185138-01. S.N.Z. is funded by a CRUK Advanced Clinician Scientist Fellowship (C60100/A23916) and supported by the NIHR Cambridge BRC (BRC-125-20014). A.G. is funded by BCN KCL-Q3. A.M.S. is funded by Birmingham CRUK Centre (C17422/A25154). J.K., L.K., T.H., A.F., D.M., C.M. and T.H. are funded by RFA-CA-17-035 (NIH; Hwang). This paper represents independent research part funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at Guy{\textquoteright}s and St Thomas{\textquoteright} NHS Foundation Trust and King{\textquoteright}s College London, supported via its BRC Genomics Research Platform. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. Funding Information: Authors listed from ** to ***are in alphabetical order. WES sequencing support was provided by the Moon Shot Cancer Genomics Laboratory, X. Song and L.D. Little, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. We thank all patients in the US, The Netherlands and the UK who have donated their data and tissue for this work. We also wish to thank all the collaborating hospitals, and in particular, pathology departments, and all persons who have helped in the process of data collection and analysis. The authors thank the registration team of the Netherlands Comprehensive Cancer Organization (IKNL) for the collection of data for the Netherlands Cancer Registry. We thank PALGA, the nationwide network and registry of histo- and cytopathology in the Netherlands, for providing pathology data and for their help in the collection of the residual patient material. We acknowledge the staff of the NKI-AVL Core Facility Molecular Pathology and Biobanking for their technical support and the staff of the NKI-AVL Genomics Core Facility and Ronald van Marion of the Erasmus University Medical Center for their sequencing support. We thank T. Hardiman and R. Kataria for their input during development of the Breakclone method. The data for the Sloane Project is based on information collected and quality assured by the PHE Population Screening Programmes. Access to the data was facilitated by the PHE Office for Data Release. We are also grateful for T. Lynch, who helped to expertly coordinate the PRECISON team at Duke University. This work was supported by Cancer Research UK and KWF Kankerbestrijding (reference C38317/A24043) and Breast Cancer Now (2014NovTAP379) with support from Walk the Walk. E.J.S. is funded by a Career Development and Innovation Cancer Award, Guys and St Thomas{\textquoteright} Charity and the Cancer Research UK King{\textquoteright}s Health Partners Centre at King{\textquoteright}s College London. T.K. is funded by a T32 Translational Genomics Fellowship. This work was supported by grants to N.E.N. by the National Cancer Institute (RO1CA240526) and the CPRIT Single Cell Genomics Center (RP180684). E.S.H. is funded by RFA-CA-17-035 (NIH), 1505-30497 (PCORI), BCRF 19-074 (BCRF), DOD BC132057 and R01 CA185138-01. S.N.Z. is funded by a CRUK Advanced Clinician Scientist Fellowship (C60100/A23916) and supported by the NIHR Cambridge BRC (BRC-125-20014). A.G. is funded by BCN KCL-Q3. A.M.S. is funded by Birmingham CRUK Centre (C17422/A25154). J.K., L.K., T.H., A.F., D.M., C.M. and T.H. are funded by RFA-CA-17-035 (NIH; Hwang). This paper represents independent research part funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at Guy{\textquoteright}s and St Thomas{\textquoteright} NHS Foundation Trust and King{\textquoteright}s College London, supported via its BRC Genomics Research Platform. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = jun,
doi = "10.1038/s41588-022-01082-3",
language = "English",
volume = "54",
pages = "850--860",
journal = "Nature genetics",
issn = "1061-4036",
publisher = "Nature Research",
number = "6",
}
