Human Gene Set: BRAUNE_GEIST_20_GENE_NOTCH_SIG_BREAST_CANCER


Standard name BRAUNE_GEIST_20_GENE_NOTCH_SIG_BREAST_CANCER
Systematic name M48357
Brief description Notch transcriptomic signature as a tool to measure the level of Notch signaling in breast cancer
Full description or abstract Dysregulated Notch signaling contributes to breast cancer development and progression, but validated tools to measure the level of Notch signaling in breast cancer subtypes and in response to systemic therapy are largely lacking. A transcriptomic signature of Notch signaling would be warranted, for example to monitor the effects of future Notch-targeting therapies and to learn whether altered Notch signaling is an off-target effect of current breast cancer therapies. In this report, we have established such a classifier, a 20-gene transcriptional signature. To generate the signature, we first identified Notch-regulated genes from six basal-like breast cancer cell lines subjected to elevated or reduced Notch signaling by culturing on immobilized Notch ligand Jagged1 or blockade of Notch by γ-secretase inhibitors, respectively. From this cadre of Notch-regulated genes, we developed candidate transcriptomic signatures that were trained on a breast cancer patient dataset (the TCGA-BRCA cohort) and a broader breast cancer cell line cohort and sought to validate in independent datasets. An optimal 20-gene transcriptomic signature was selected. We validated the signature on two independent patient datasets (METABRIC and Oslo2), and it showed an improved coherence score and tumor specificity compared with previously published signatures. Furthermore, the signature score was particularly high for basal-like breast cancer, indicating an enhanced level of Notch signaling in this subtype. The signature score was increased after neoadjuvant treatment in the PROMIX and BEAUTY patient cohorts, and a lower signature score generally correlated with better clinical outcome. The signature will be a valuable tool to evaluate the response of future Notch-targeting therapies for breast cancer, to learn about potential effects on Notch signaling from conventional breast cancer therapies and to better stratify patients for therapy considerations.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 38172915   Authors: Braune EB,Geist F,Tang X,Kalari K,Boughey J,Wang L,Leon-Ferre RA,D'Assoro AB,Ingle JN,Goetz MP,Kreis J,Wang K,Foukakis T,Seshire A,Wienke D,Lendahl U
Exact source https://github.com/KarolinskaMerck/NotchBRCASignature (and Fig 3A, Table S3)
Related gene sets (show 71 gene sets from the same authors)
External links https://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-023-01757-7
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Source species Homo sapiens
Contributed by Eike-Benjamin Braune (Karolinska Institutet)
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identifier namespace		 HUMAN_GENE_SYMBOL
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GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)
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Version history 2024.1.Hs: First Introduced.

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