期刊
JOURNAL OF PATHOLOGY
卷 255, 期 1, 页码 1-15出版社
WILEY
DOI: 10.1002/path.5705
关键词
rhabdoid tumours; SCCOHT; SMARCA4; SMARCB1; SMARCA2; SWI; SNF; paediatric cancer; methylation; transcriptomics; epigenetics
资金
- Saint Baldrick Foundation
- Federation Enfants et Sante
- Societe Francaise de Lutte contre les Leucemies et Cancers de l'Enfant et de l'Adolescent (SFCE)
- Association pour la Recherche contre le Cancer (ARC)
- Ligue Nationale Contre le Cancer
- Institut National du Cancer [PLBIO 2017-02-ICR1]
- Deutsche Krebshilfe
- Wilhelm Sander Stiftung
- Fordergemeinschaft Kinderkrebszentrum Hamburg
- DFG
ECRTSMARCA4 and ECRTSMARCB1 share similar clinical, pathological, and genomic features, with ECRTSMARCA4 showing closer relationship to SCCOHT. Lack of SMARCA4 and SMARCA2 expression at the protein level is observed in ECRTSMARCA4.
Extracranial rhabdoid tumours (ECRTs) are an aggressive malignancy of infancy and early childhood. The vast majority of cases demonstrate inactivation of SMARCB1 (ECRTSMARCB1) on a background of a remarkably stable genome, a low mutational burden, and no other recurrent mutations. Rarely, ECRTs can harbour the alternative inactivation of SMARCA4 (ECRTSMARCA4) instead of SMARCB1. However, very few ECRTSMARCA4 cases have been published to date, and a systematic characterization of ECRTSMARCA4 is missing from the literature. In this study, we report the clinical, pathological, and genomic features of additional cases of ECRTSMARCA4 and show that they are comparable to those of ECRTSMARCB1. We also assess whether ECRTSMARCB1, ECRTSMARCA4, and small cell carcinomas of the ovary, hypercalcaemic type (SCCOHT) represent distinct or overlapping entities at a molecular level. Using DNA methylation and transcriptomics-based tumour classification approaches, we demonstrate that ECRTSMARCA4 display molecular features intermediate between SCCOHT and ECRTSMARCB1; however, ECRTSMARCA4 appear to be more closely related to SCCOHT by DNA methylation. Conversely, both transcriptomics and DNA methylation show a larger gap between SCCOHT and ECRTSMARCB1, potentially supporting their continuous separate classification. Lastly, we show that ECRTSMARCA4 display concomitant lack of SMARCA4 (BRG1) and SMARCA2 (BRM) expression at the protein level, similar to what is seen in SCCOHT. Overall, these results expand our knowledge on this rare tumour type and explore the similarities and differences among entities from the 'rhabdoid tumour' spectrum. (c) 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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