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Treatment hope after rare cancer origin discovered

Thursday March 4th 2021

The origin of a rare childhood cancer has been discovered – and a possible drug treatment.

Researchers at the Wellcome Sanger Institute, the Princess Máxima Centre for Paediatric Oncology in the Netherlands, and collaborators, found that malignant rhabdoid tumour (MRT) arises from developmental cells in the neural crest whose maturation is blocked by a genetic defect.

Thanks to the discovery, the team also identified two drugs that could overcome the block and resume normal development.

The study, published in the latest edition of Nature Communications, involved the whole genome sequencing of two MRT cases alongside normal tissues.

The team went on to conduct phylogenetic analyses of the somatic mutations in the diseased and healthy tissue to reconstruct the timeline of normal and abnormal development.

They found MRT develops from progenitor cells before they become Schwann cells, due to a mutation in the SMARCB1 gene. This mutation blocks the normal development of these cells and these can then go on to form MRT.

Researchers at the Princess Máxima Centre for Paediatric Oncology inserted the intact SMARCB1 gene into patient derived MRT organoids, which resulted in it overcoming the maturation block that had prevented normal development and led to cancer.

Co-lead study author Dr Jarno Drost, of the Princess Máxima Centre for Paediatric Oncology, said: “To be able to identify where malignant rhabdoid tumour (MRT) comes from for the first time is an important step in being able to treat this disease, but to confirm that it is possible to overcome the genetic flaw that can cause these tumours is incredibly exciting.

“The fact that two drugs already exist that we think can be used to treat the disease gives us hope that we can improve outcomes for children diagnosed with MRT.”

Dr Sam Behjati, co-lead study author from the Wellcome Sanger Institute, said: “We began our enquiry into the origins of malignant rhabdoid tumours in late 2019, so we have gone from hypothesis to discovery of origin to possible treatments for the disease in just over a year. This was possible due to all the leading-edge tools available to us, from organoid technology to single-cell mRNA sequencing to drug screen databases.”

Professor Richard Grundy, chair of the Children’s Cancer and Leukaemia Group, said the findings give new hope to children with MRT.

Custers L, Khabirova , Coorens THH et al. (2021). Somatic mutations and single cell transcriptomes reveal the root of malignant rhabdoid tumours. Nature Communications 3 March 2021

[abstract]

Tags: Cancer | Child Health | Europe | Genetics | Pharmaceuticals | UK News

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