Clinical and genomic implications of luminal and basal subtypes across carcinomas

Purpose: Carcinomas originate from epithelial tissues, tumor types, with luminal B tumors falling between the two. which have apical (luminal) and basal orientations. The Basal tumors had the highest rates of TP53 and RB1 mutations degree of luminal versus basal differentiation in cancer has and copy number loss. Luminal breast, cervical, ovarian, and been shown to be biologically important in some carcinomas endometrial tumors had increased ESR1 expression, and lumi- and impacts treatment response. nal prostate, breast, cervical, and bladder tumors had increased Experimental Design: Although prior studies have androgen receptor (AR) expression. Furthermore, luminal B focused on individual cancer types, we used a modified tumors had the highest rates of AR and ESR1 mutations and clinical-grade classifier (PAM50) to subtype 8,764 tumors had increased sensitivity in vitro to bicalutamide across 22 different carcinomas into luminal A, luminal B, and tamoxifen. Luminal B tumors were more sensitive to and basal-like tumors. gemcitabine, and basal tumors were more sensitive to Results: We found that all epithelial tumors demonstrated docetaxel. similar gene expression–based luminal/basal subtypes. As Conclusions: This first pan-carcinoma luminal/basal sub-expected, basal-like tumors were associated with increased typing across epithelial tumors reveals global similarities expression of the basal markers KRT5/6 and KRT14, and across carcinomas in the transcriptome, genome, clinical luminal-like tumors were associated with increased expression outcomes, and drug sensitivity, emphasizing the biological of the luminal markers KRT20. Luminal A tumors consistently and translational importance of these luminal versus basal had improved outcomes compared with basal across many subtypes.