EFM-192B

Molecular Subtyping of BC Cell Lines Separate Basal-like from Luminal BC Models

Selecting the most representative breast-cancer (BC) cell line is hampered by incomplete molecular annotation. Pommerenke et al. performed deep profiling (RNA-seq, mutation calling, immunoblotting) of 29 authenticated BC lines to create a comprehensive reference map that links each line to clinical BC subtypes and reveals novel genetic drivers.

Transcriptome-wide analysis revealed that all basal-like cell lines clustered in group B and were classified as TNBCs, while luminal-expressing cell lines (ESR1⁺, FOXA1⁺) primarily clustered in group A (Fig. 1B). Notably, ERBB2-high cell lines (>200 tpm) including BT-474, EFM-192 variants, IPH-926, JIMT-1, MDA-MB-453, and SK-BR-3 did not form a distinct branch but localized within the luminal arm. All AR⁺ cell lines were confined to the luminal/cluster A group, though JIMT-1 exhibited a mixed phenotype, clustering as HER2⁺ in group B despite luminal features. PAM50 analysis failed to sub-classify luminal cell lines into LumA and LumB, consistent with previous BC cell line studies. We therefore examined miR-99a-5p, a LumA-associated tumor suppressor microRNA. qPCR revealed strong expression in JIMT-1 and T-47D, but absence in EFM-19, EFM-192A, ETCC-007, KPL-1, MCF-7, MDA-MB-453, and MFM-223 (Fig. 2). However, intra-patient heterogeneity was evident: EFM-192B and EFM-192C expressed miR-99a-5p whereas EFM-192A did not, suggesting clonal variation weakens its discriminatory power. Given evidence for subtype admixture in BC, we refrained from LumA/LumB assignment based on transcriptome or miR-99a-5p data alone.