c-MYC overexpression induces choroid plexus papillomas through a T-cell mediated inflammatory mechanism.
Ashirwad MerveXinyu ZhangNicola PomellaSerena AcquatiJoerg D HoeckAnaelle DumasGabriel RosserYichen LiJennie JeyapalanSilvia VicenziQianhai FanZeng Jie YangArianna SabòDenise SheerAxel BehrensSilvia MarinoPublished in: Acta neuropathologica communications (2019)
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.
Keyphrases
- ultrasound guided
- mouse model
- oxidative stress
- cell proliferation
- wild type
- healthcare
- endothelial cells
- anti inflammatory drugs
- transcription factor
- young adults
- gene expression
- randomized controlled trial
- risk factors
- dna methylation
- bone marrow
- rna seq
- stem cells
- machine learning
- electronic health record
- big data
- multiple sclerosis
- single molecule
- double blind