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Translational Genomics of Malignant Rhabdoid Tumours: Current Impact and Future Possibilities

Lookup NU author(s): Dr Martina Finetti, Yura Grabovska, Professor Simon Bailey, Dr Daniel Williamson



This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


Malignant Rhabdoid Tumours (MRT) are the quintessential example of an epigenetic cancer. Mutation of a single gene, SMARCB1 or more rarely SMARCA4, is capable of causing one of the most aggressive and lethal cancers of early childhood and infancy. SMARCB1 encodes a core subunit of the SWI/SNF complex and its mutation evokes genome-wide downstream effects which may be counteracted therapeutically. Here we review and discuss the use of translational genomics in the study of MRT biology and the ways in which this has impacted clinical practice or may do so in the future. First, the diagnosis and definition of MRT and the transition from a histopathological to a molecular definition. Second, epigenetic and transcriptomic subgroups within MRT, their defining features and potential prognostic or therapeutic significance. Third, functional genomic studies of MRT by mouse modelling and forced re-expression of SMARCB1 in MRT cells. Fourth, studies of underlying epigenetic mechanisms (e.g. EZH2, HDACs) or deregulated kinases (e.g. PDGFR, FGFR1) and the potential therapeutic opportunities these provide. Finally, we discuss likely future directions and proffer opinion on how future translational genomics should be integrated into future biological/clinical studies to select and evaluate the best anti-MRT therapeutic agents.

Publication metadata

Author(s): Finetti MA, Grabovska Y, Bailey S, Williamson D

Publication type: Article

Publication status: Published

Journal: Seminars in Cancer Biology

Year: 2020

Volume: 61

Pages: 31-40

Print publication date: 01/04/2020

Online publication date: 07/01/2020

Acceptance date: 16/12/2019

Date deposited: 29/01/2020

ISSN (print): 1044-579X

ISSN (electronic): 1096-3650

Publisher: Elsevier


DOI: 10.1016/j.semcancer.2019.12.017


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