Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London, E1 2AT, UK.
Adult Stem Cell Laboratory, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.
Acta Neuropathol Commun. 2019 May 29;7(1):95. doi: 10.1186/s40478-019-0739-x.
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.
脉络丛肿瘤（CPTs）占儿童脑肿瘤的 2-5%。它们可以沿着中枢神经系统扩散，并且在治疗后可能会复发。目前对于其形成的分子机制知之甚少，只有少数高保真的 p53 缺陷恶性 CPT 的小鼠模型可用。我们在这里显示，脉络丛上皮细胞中的 c-MYC 过表达会在小鼠模型中诱导 T 细胞炎症依赖性脉络丛乳头瘤。我们证明 c-MYC 在相当一部分人类脉络丛肿瘤中表达，并且这群肿瘤的特征是炎症转录组和大量炎症浸润。在复合突变小鼠中，在免疫缺陷背景下过表达 c-MYC 可降低 CPP 的发生率并减少肿瘤体积。最后，在 CPP 荷瘤小鼠中耗尽 T 细胞也观察到肿瘤体积减小。我们的数据提出了这样一种可能性，即表达 c-MYC 的良性脉络丛肿瘤可能可以通过抗炎药物进行医学治疗。
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