The claudin-low subtype.

We recently described a group of single nucleotide polymorphism specifically associated with molecular subtype in breast cancer, together indicating activity at specific genomic positions was associated with the tumorigenesis and subtype selection during transformation of the breast. We previously described clusters of SNPs associated with the basal subtype at 5q14 (7-15), the luminal A subtype at 16p12 (16, 17) and 16q21-24 (18-25), the luminal B subtype at 12q14.3 - 12q15 (26-33), and the HER2+ subtype at 17q12 (34-38) and 17q21.1 - 17q.23.1 (39-42). The claudin-low subtype was enriched for SNPs at multiple loci contained within 1q24-1q25. We demonstrate here that claudin-enriched TNBCs display enhanced growth factor signaling characterized by activation of the fibroblast growth factor receptors FGFR1 and FGFR2, and insulin-like growth factor binding proteins (IGFBPs) IGFBP3 and IGFBP7. We demonstrate here that Claudin-enriched TNBCs are enriched for expression of the matrix metalloproteinase MMP14, carry the GPR161+ GPR19+ GPR176+ signature and are Claudin-12+.