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Merve A , Zhang X , Pomella N , Acquati S , Hoeck JD , Dumas A , Rosser G , Li Y , Jeyapalan J , Vicenzi S , Fan Q , Yang ZJ , Sabo A , Sheer D , Behrens A , Marino S
c-MYC overexpression induces choroid plexus papillomas through a T-cell mediated inflammatory mechanism
Acta Neuropathol Commun. 2019 May 29;7(1) :95
PMID: 31142360 PMCID: PMC6540455 URL: https://www.ncbi.nlm.nih.gov/pubmed/31142360
AbstractChoroid plexus tumours (CPTs) account for 2-5% of brain tumours in children. They can spread along the neuraxis and can recur after treatment. Little is known about the molecular mechanisms underlying their formation and only few high fidelity mouse models of p53-deficient malignant CPTs are available.We show here that c-MYC overexpression in the choroid plexus epithelium induces T-cell inflammation-dependent choroid plexus papillomas in a mouse model. We demonstrate that c-MYC is expressed in a substantial proportion of human choroid plexus tumours and that this subgroup of tumours is characterised by an inflammatory transcriptome and significant inflammatory infiltrates. In compound mutant mice, overexpression of c-MYC in an immunodeficient background led to a decreased incidence of CPP and reduced tumour bulk. Finally, reduced tumour size was also observed upon T-cell depletion in CPP-bearing mice. Our data raise the possibility that benign choroid plexus tumours expressing c-MYC could be amenable to medical therapy with anti-inflammatory drugs.
Notes2051-5960 Merve, Ashirwad Zhang, Xinyu Pomella, Nicola Acquati, Serena Hoeck, Joerg D Dumas, Anaelle Rosser, Gabriel Li, Yichen Jeyapalan, Jennie Vicenzi, Silvia Fan, Qianhai Yang, Zeng Jie Sabo, Arianna Sheer, Denise Behrens, Axel Marino, Silvia ORCID: http://orcid.org/0000-0002-9612-2883 G0800020/Medical Research Council UK CoE QMUL/Brain Tumour Research Cl/nihr Journal Article England Acta Neuropathol Commun. 2019 May 29;7(1):2. doi: 10.1186/s40478-019-0739-x.