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

Authors :
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
King LM
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
Thompson AM
Wesseling J
Sawyer EJ
Source :
Nature genetics [Nat Genet] 2022 Jun; Vol. 54 (6), pp. 850-860. Date of Electronic Publication: 2022 Jun 09.
Publication Year :
2022

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.<br /> (© 2022. The Author(s).)

Details

Language :
English
ISSN :
1546-1718
Volume :
54
Issue :
6
Database :
MEDLINE
Journal :
Nature genetics
Publication Type :
Academic Journal
Accession number :
35681052
Full Text :
https://doi.org/10.1038/s41588-022-01082-3