Exploiting Wnt expression to generate a biomarker for colorectal cancer stratification скачать в хорошем качестве

Exploiting Wnt expression to generate a biomarker for colorectal cancer stratification

To cite: Kleeman SO, Koelzer VH, Jones HJ, et al. Gut 2020;69:1092-1103. Read the full article here: http://dx.doi.org/10.1136/gutjnl-2019.... Objective: Pathological Wnt pathway activation is a conserved hallmark of colorectal cancer. Wnt-activating mutations can be divided into: i) ligand-independent (LI) alterations in intracellular signal transduction proteins (Adenomatous polyposis coli, β-catenin), causing constitutive pathway activation and ii) ligand-dependent (LD) mutations affecting the synergistic R-Spondin axis (RNF43, RSPO-fusions) acting through amplification of endogenous Wnt signal transmembrane transduction. Our aim was to exploit differential Wnt target gene expression to generate a mutation-agnostic biomarker for LD tumours. Conclusions: Epigenetic suppression of appropriate Wnt negative feedback loops is selectively advantageous in LD tumours and differential AXIN2 expression in LD/LI lesions can be exploited as a molecular biomarker. Distinguishing between LD/LI tumour types is important; patients with LD tumours retain sensitivity to Wnt ligand inhibition and may be stratified at diagnosis to clinical trials of Porcupine inhibitors. Acknowledgement: Music: Summer - Bensound https://www.bensound.com Support by RFM - NCM: https://bit.ly/2xGHypM