c-MYC overexpression induces choroid plexus papillomas through a T-cell mediated inflammatory mechanism

Ashirwad Merve, Xinyu Zhang, Nicola Pomella, Serena Acquati, Joerg D. Hoeck, Anaelle Dumas, Gabriel Rosser, Yichen Li, Jennie Jeyapalan, Silvia Vicenzi, Qianhai Fan, Zeng Jie Yang, Arianna Sabò, Denise Sheer, Axel Behrens, Silvia Marino

Research output: Contribution to journalArticle

Abstract

Choroid 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.

Original languageEnglish
Number of pages1
JournalActa neuropathologica communications
Volume7
Issue number1
DOIs
Publication statusPublished - May 29 2019

Keywords

  • C-MYC
  • Choroid plexus tumours
  • Inflammation
  • Mouse models

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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    Merve, A., Zhang, X., Pomella, N., Acquati, S., Hoeck, J. D., Dumas, A., Rosser, G., Li, Y., Jeyapalan, J., Vicenzi, S., Fan, Q., Yang, Z. J., Sabò, A., Sheer, D., Behrens, A., & Marino, S. (2019). c-MYC overexpression induces choroid plexus papillomas through a T-cell mediated inflammatory mechanism. Acta neuropathologica communications, 7(1). https://doi.org/10.1186/s40478-019-0739-x