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- Comprehensive characterization of claudin-low breast tumors reflects the impact of the cell-of-origin on cancer evolution
Comprehensive characterization of claudin-low breast tumors reflects the impact of the cell-of-origin on cancer evolution
Auteurs
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, Alain Puisieux
Résumé
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
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