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bioRxiv · 10.1101/756411

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

Fougner, C.·Bergholtz, H.·Norum, J. H.·Sorlie, T.
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Abstract

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 were 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 reflected characteristics of their intrinsic subtype. Finally, we have developed an alternative method for identifying claudin-low tumors and thereby uncovered 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.\n\nContact informationC.F. christian.fougner@rr-research.no\n\nH.B. helga.bergholtz@rr-research.no\n\nJ.H.N. jens.henrik.norum@rr-research.no\n\nT.S. therese.sorlie@rr-research.no

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Fougner, C., Bergholtz, H., Norum, J. H., Sorlie, T.. 2019-09-09. Re-definition of claudin-low as a breast cancer phenotype. https://doi.org/10.1101/756411

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