Re-definition of claudin-low as a breast cancer phenotype.

Christian Fougner, Helga Bergholtz, Jens Henrik Norum, Therese Sørlie

Nature communications 2020 Apr 14

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The claudin-low breast cancer subtype is defined by gene expression characteristics and encompasses a remarkably diverse range of breast tumors. Here, we investigate genomic, transcriptomic, and clinical features of claudin-low breast tumors. We show that claudin-low is not simply a subtype analogous to the intrinsic subtypes (basal-like, HER2-enriched, luminal A, luminal B and normal-like) as previously portrayed, but is a complex additional phenotype which may permeate breast tumors of various intrinsic subtypes. Claudin-low tumors are distinguished by low genomic instability, mutational burden and proliferation levels, and high levels of immune and stromal cell infiltration. In other aspects, claudin-low tumors reflect characteristics of their intrinsic subtype. Finally, we explore an alternative method for identifying claudin-low tumors and thereby uncover potential weaknesses in the established claudin-low classifier. In sum, these findings elucidate the heterogeneity in claudin-low breast tumors, and substantiate a re-definition of claudin-low as a cancer phenotype.

Citation

Christian Fougner, Helga Bergholtz, Jens Henrik Norum, Therese Sørlie. Re-definition of claudin-low as a breast cancer phenotype. Nature communications. 2020 Apr 14;11(1):1787