Genomic analysis defines clonal relationships of ductal carcinoma in situ and recurrent invasive breast cancer

Esther H. Lips; Tapsi Kumar; Anargyros Megalios; Lindy L. Visser; Michael Sheinman; Angelo Fortunato; Vandna Shah; Marlous Hoogstraat; Emi Sei; Diego Mallo; Maria Roman-escorza; Ahmed A. Ahmed; Mingchu Xu; Alexandra W. Van Den Belt-dusebout; Wim Brugman; Anna K. Casasent; Karen Clements; Helen R. Davies; Liping Fu; Anita Grigoriadis; Timothy M. Hardman; Marielle Krete; Petra Kristel; Michiel De Maaker; Carlo C. Maley; Jeffrey R. Marks; Brian A. Menegaz; Lennart Mulder; Frank Nieboer; Salpie Nowinski; Sarah Pinder; Jelmar Quist; Carolina Salinas-souza; Michael Schaapveld; Marjanka K. Schmidt; Abeer M. Shaaban; Rana Shami; Mathini Sridharan; John Zhang; Hilary Stobart; Deborah Collyar; Serena Nik-zainal; Lodewyk F. A. Wessels; E. Shelley Hwang; Nicholas E. Navin; P. Andrew Futreal; P. Andrew Futreal; E. Shelley Hwang; Jos Jonkers; Jacco; Fariba Behbod; Daniel Rea; Proteeti Bhattacharjee; Donna Pinto; Ellen Verschuur; Marja Van Oirsouw; Alastair M. Thompson; Jelle Wesseling; Elinor J. Sawyer

doi:10.1038/s41588-022-01082-3

Genomic analysis defines clonal relationships of ductal carcinoma in situ and recurrent invasive breast cancer

Esther H. Lips, Tapsi Kumar, Anargyros Megalios, Lindy L. Visser, Michael Sheinman, Angelo Fortunato, Vandna Shah, Marlous Hoogstraat, Emi Sei, Diego Mallo, Maria Roman-escorza, Ahmed A. Ahmed, Mingchu Xu, Alexandra W. Van Den Belt-dusebout, Wim Brugman, Anna K. Casasent, Karen Clements, Helen R. Davies, Liping Fu, Anita GrigoriadisTimothy M. Hardman, Marielle Krete, Petra Kristel, Michiel De Maaker, Carlo C. Maley, Jeffrey R. Marks, Brian A. Menegaz, Lennart Mulder, Frank Nieboer, Salpie Nowinski, Sarah Pinder, Jelmar Quist, Carolina Salinas-souza, Michael Schaapveld, Marjanka K. Schmidt, Abeer M. Shaaban, Rana Shami, Mathini Sridharan, John Zhang, Hilary Stobart, Deborah Collyar, Serena Nik-zainal, Lodewyk F. A. Wessels, E. Shelley Hwang, Nicholas E. Navin, P. Andrew Futreal, P. Andrew Futreal, E. Shelley Hwang, Jos Jonkers, Jacco, Fariba Behbod, Daniel Rea, Proteeti Bhattacharjee, Donna Pinto, Ellen Verschuur, Marja Van Oirsouw, Alastair M. Thompson, Jelle Wesseling, Elinor J. Sawyer

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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.

Original language	English
Pages (from-to)	850-860
Number of pages	11
Journal	Nature Genetics
Volume	54
Issue number	6
Early online date	9 Jun 2022
DOIs	https://doi.org/10.1038/s41588-022-01082-3
Publication status	Published - Jun 2022

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Lips, E. H., Kumar, T., Megalios, A., Visser, L. L., Sheinman, M., Fortunato, A., Shah, V., Hoogstraat, M., Sei, E., Mallo, D., Roman-escorza, M., Ahmed, A. A., Xu, M., Van Den Belt-dusebout, A. W., Brugman, W., Casasent, A. K., Clements, K., Davies, H. R., Fu, L., ... Sawyer, E. J. (2022). Genomic analysis defines clonal relationships of ductal carcinoma in situ and recurrent invasive breast cancer. Nature Genetics, 54(6), 850-860. https://doi.org/10.1038/s41588-022-01082-3

@article{cacaa4c3a84d4423b32dd24798b29cd5,

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 = "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 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 Jos Jonkers and Jacco and Fariba Behbod and Daniel Rea and Proteeti Bhattacharjee and Donna Pinto and Ellen Verschuur and \{Van Oirsouw\}, Marja and Thompson, \{Alastair M.\} and Jelle Wesseling and Sawyer, \{Elinor J.\}",

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 Publishing Group",

number = "6",

}

Lips, EH, Kumar, T, Megalios, A, Visser, LL, Sheinman, M, Fortunato, A, Shah, V, Hoogstraat, M, Sei, E, Mallo, D, Roman-escorza, M, Ahmed, AA, Xu, M, Van Den Belt-dusebout, AW, Brugman, W, Casasent, AK, Clements, K, Davies, HR, Fu, L, Grigoriadis, A, Hardman, TM, Krete, M, Kristel, P, De Maaker, M, Maley, CC, Marks, JR, Menegaz, BA, Mulder, L, Nieboer, F, Nowinski, S, Pinder, S, Quist, J, Salinas-souza, C, Schaapveld, M, Schmidt, MK, Shaaban, AM, Shami, R, Sridharan, M, Zhang, J, Stobart, H, Collyar, D, Nik-zainal, S, Wessels, LFA, Hwang, ES, Navin, NE, Futreal, PA, Futreal, PA, Hwang, ES, Jonkers, J, Jacco, Behbod, F, Rea, D, Bhattacharjee, P, Pinto, D, Verschuur, E, Van Oirsouw, M, Thompson, AM, Wesseling, J & Sawyer, EJ 2022, 'Genomic analysis defines clonal relationships of ductal carcinoma in situ and recurrent invasive breast cancer', Nature Genetics, vol. 54, no. 6, pp. 850-860. https://doi.org/10.1038/s41588-022-01082-3

TY - JOUR

T1 - Genomic analysis defines clonal relationships of ductal carcinoma in situ and recurrent invasive breast cancer

AU - Lips, Esther H.

AU - Kumar, Tapsi

AU - Megalios, Anargyros

AU - Visser, Lindy L.

AU - Sheinman, Michael

AU - Fortunato, Angelo

AU - Shah, Vandna

AU - Hoogstraat, Marlous

AU - Sei, Emi

AU - Mallo, Diego

AU - Roman-escorza, Maria

AU - Ahmed, Ahmed A.

AU - Xu, Mingchu

AU - Van Den Belt-dusebout, Alexandra W.

AU - Brugman, Wim

AU - Casasent, Anna K.

AU - Clements, Karen

AU - Davies, Helen R.

AU - Fu, Liping

AU - Grigoriadis, Anita

AU - Hardman, Timothy M.

AU - Krete, Marielle

AU - Kristel, Petra

AU - De Maaker, Michiel

AU - Maley, Carlo C.

AU - Marks, Jeffrey R.

AU - Menegaz, Brian A.

AU - Mulder, Lennart

AU - Nieboer, Frank

AU - Nowinski, Salpie

AU - Pinder, Sarah

AU - Quist, Jelmar

AU - Salinas-souza, Carolina

AU - Schaapveld, Michael

AU - Schmidt, Marjanka K.

AU - Shaaban, Abeer M.

AU - Shami, Rana

AU - Sridharan, Mathini

AU - Zhang, John

AU - Stobart, Hilary

AU - Collyar, Deborah

AU - Nik-zainal, Serena

AU - Wessels, Lodewyk F. A.

AU - Hwang, E. Shelley

AU - Navin, Nicholas E.

AU - Futreal, P. Andrew

AU - Hwang, E. Shelley

AU - Jonkers, Jos

AU - Jacco, null

AU - Behbod, Fariba

AU - Rea, Daniel

AU - Bhattacharjee, Proteeti

AU - Pinto, Donna

AU - Verschuur, Ellen

AU - Van Oirsouw, Marja

AU - Thompson, Alastair M.

AU - Wesseling, Jelle

AU - Sawyer, Elinor J.

PY - 2022/6

Y1 - 2022/6

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85132254027

U2 - 10.1038/s41588-022-01082-3

DO - 10.1038/s41588-022-01082-3

M3 - Article

SN - 1061-4036

VL - 54

SP - 850

EP - 860

JO - Nature Genetics

JF - Nature Genetics

IS - 6

ER -

Genomic analysis defines clonal relationships of ductal carcinoma in situ and recurrent invasive breast cancer

Abstract

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