Fig4: CNH tumors. a Survival analysis across two independent datasets shows significantly worse outcome for the CNH Luminal A tumors. b Unbiased enrichment analysis of genomic alterations found CNH tumors to be enriched for TP53 mutations, focal amplification of MYC, 5q loss, 20q gain, and depleted for PIK3CA mutations. c Differential expression analysis shows that significantly up-regulated genes in CNH tumors are enriched for regulators of mitosis and Aurora kinase pathway components. The heatmap shows all genes that are differentially expressed in CNH tumors when compared to other Luminal A samples (red indicates high expression, green low expression). Aurora kinase is a mitotic serine/threonine kinase that phosphorylates multiple proteins including PLK1 and Cdc25; it is required for CDK1 activation and regulates mitotic events

Mentions: The characterization of Luminal A tumors provided so far clearly identifies distinct subgroups within this tumor subtype, whose clinical relevance needs to be addressed now. The large dataset analyzed by Curtis et al. [12] has extensive clinical follow-up, enabling a reliable survival analysis. Kaplan–Meier analysis showed significantly different disease survival within the Luminal A subgroups (log-rank p = 0.015, Fig. S4). In particular, the CNH subgroup had significantly worse outcome (log-rank p = 4.6E−5, Fig. 4a) despite receiving similar treatments (Table S3). We validated the poor prognosis for the CNH tumors in an independent dataset consisting of 77 Luminal A tumors from three different cohorts [19] (log-rank p = 0.003, Fig. 4b; Table S4).Fig. 4