Re-definition of claudin-low as a breast cancer phenotype
Re-definition of claudin-low as a breast cancer phenotype
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DOI：
10.1038/s41467-020-15574-5
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发表时间：
2020-04-14
影响因子：
16.6
通讯作者：
Sorlie, Therese
中科院分区：
文献类型：
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作者：
Fougner, Christian;Bergholtz, Helga;Sorlie, Therese
claudin低乳腺癌亚型由基因表达特征定义，包括非常多样化的乳腺肿瘤。在这里，我们调查基因组，转录组学和临床特征的claudin低乳腺肿瘤。我们表明，claudin-low不是简单的亚型类似于内在亚型（基底细胞样，HER 2富集，管腔A，管腔B和正常样）如前所述，但它是一个复杂的额外的表型，可能会渗透到各种内在亚型的乳腺肿瘤。低密蛋白肿瘤的特征在于低基因组不稳定性、突变负荷和增殖水平以及高水平的免疫和基质细胞浸润。在其他方面，低密蛋白肿瘤反映了其内在亚型的特征。最后，我们探索了一种用于识别低密蛋白肿瘤的替代方法，从而揭示了已建立的低密蛋白分类器的潜在弱点。总之，这些发现阐明了低密蛋白乳腺肿瘤的异质性，并证实了低密蛋白作为癌症表型的重新定义。在乳腺癌中，低密蛋白乳腺癌亚型是非常多样化的。在这里，作者提出claudin-low不是一种经典的内在乳腺癌亚型，而是一种复杂的额外表型，可以在内在亚型中发生。
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. In breast cancer, the claudin-low breast cancer subtype is remarkably diverse. Here, the authors propose that claudin-low is not a classical intrinsic breast cancer subtype, but rather a complex additional phenotype that can occur across intrinsic subtypes.