Comprehensive characterization of claudin-low breast tumors reflects the impact of the cell-of-origin on cancer evolution

Roxane M. Pommier, Amélien Sanlaville, Laurie Tonon, Janice Kielbassa, Emilie Thomas, Anthony Ferrari, Anne-Sophie Sertier, Frédéric Hollande, Pierre Martinez, Agnès Tissier, Anne-Pierre Morel, Maria Ouzounova and Alain Puisieux ()
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Roxane M. Pommier: Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Equipe Labellisée Ligue contre le Cancer
Amélien Sanlaville: Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Equipe Labellisée Ligue contre le Cancer
Laurie Tonon: Plateforme de bioinformatique Gilles Thomas, Centre Léon Bérard
Janice Kielbassa: Plateforme de bioinformatique Gilles Thomas, Centre Léon Bérard
Emilie Thomas: Plateforme de bioinformatique Gilles Thomas, Centre Léon Bérard
Anthony Ferrari: Plateforme de bioinformatique Gilles Thomas, Centre Léon Bérard
Anne-Sophie Sertier: Plateforme de bioinformatique Gilles Thomas, Centre Léon Bérard
Frédéric Hollande: The University of Melbourne, Victorian Comprehensive Cancer Centre
Pierre Martinez: Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Equipe Labellisée Ligue contre le Cancer
Agnès Tissier: Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Equipe Labellisée Ligue contre le Cancer
Anne-Pierre Morel: Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Equipe Labellisée Ligue contre le Cancer
Maria Ouzounova: Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Equipe Labellisée Ligue contre le Cancer
Alain Puisieux: Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Equipe Labellisée Ligue contre le Cancer

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: Abstract Claudin-low breast cancers are aggressive tumors defined by the low expression of key components of cellular junctions, associated with mesenchymal and stemness features. Although they are generally considered as the most primitive breast malignancies, their histogenesis remains elusive. Here we show that this molecular subtype of breast cancers exhibits a significant diversity, comprising three main subgroups that emerge from unique evolutionary processes. Genetic, gene methylation and gene expression analyses reveal that two of the subgroups relate, respectively, to luminal breast cancers and basal-like breast cancers through the activation of an EMT process over the course of tumor progression. The third subgroup is closely related to normal human mammary stem cells. This unique subgroup of breast cancers shows a paucity of genomic aberrations and a low frequency of TP53 mutations, supporting the emerging notion that the intrinsic properties of the cell-of-origin constitute a major determinant of the genetic history of tumorigenesis.

Date: 2020
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DOI: 10.1038/s41467-020-17249-7

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