BioProject

In breast cancer, gene expression analyses have defined five tumor subtypes, each of which has unique biologic and prognostic features. More...

In breast cancer, gene expression analyses have defined five tumor subtypes, each of which has unique biologic and prognostic features. Here, we characterize the recently identified claudin-low tumor subtype as showing low to absent expression of luminal differentiation markers, high enrichment for epithelial-to-mesenchymal transition markers, immune response genes, and cancer stem cell–like features. Clinically, most claudin-low tumors are poorprognosis estrogen receptor–negative, progesterone receptor–negative, and human epidermal growth factor receptor 2–negative (triple-negative) invasive ductal carcinomas with a high frequency of metaplastic and medullary differentiation. They also have a response rate to standard preoperative chemotherapy that is intermediate between that of basal-like and luminal tumors. Moreover, we show that a group of highly used breast cancer cell lines, and several genetically engineered mouse models, express the claudin-low phenotype. Finally, we confirm that a prognostically relevant differentiation hierarchy exists across all breast cancers in which the claudin-low subtype most closely resembles the mammary epithelial stem cell. These results should help to improve our understanding of the biologic heterogeneity of breast cancer and provide tools for the further evaluation of the unique biology of claudin-low tumors and cell lines. Overall design: We created a large genomic data set by combining three of our previously published data sets (Herschkowitz et al., Hennessy et al., Parker et al.) and included 39 new tumor samples [n = 337; UNC337). In addition, we expression profiled mammospheres (MMS) obtained from 14 reduction mammoplasties. Finally, we FAC sorted and expression profiled subpopulations from the following cell lines: MCF-7, SUM149PT and SUM159PT. Less...