SMARCA4-deficient rhabdoid tumours show intermediate molecular features between SMARCB1-deficient rhabdoid tumours and small cell carcinomas of the ovary, hypercalcaemic type.

Fiche publication

Date publication

mai 2021

Journal

The Journal of pathology

Auteurs

Membres identifiés du Cancéropôle Est :
Pr ENTZ-WERLE Natacha

Tous les auteurs :
Andrianteranagna M, Cyrta J, Masliah-Planchon J, Nemes K, Corsia A, Leruste A, Holdhof D, Kordes U, Orbach D, Corradini N, Entz-Werle N, Pierron G, Castex MP, Brouchet A, Weingertner N, Ranchère D, Fréneaux P, Delattre O, Bush J, Leary A, Frühwald MC, Schüller U, Servant N, Bourdeaut F

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/33999421

Résumé

Extracranial rhabdoid tumours (ECRT) are an aggressive malignancy of infancy and early childhood. The vast majority of cases demonstrate inactivation of SMARCB1 (ECRT ) on a background of a remarkably stable genome, a low mutational burden, and no other recurrent mutations. Rarely, ECRT can harbour the alternative inactivation of SMARCA4 (ECRT ) instead of SMARCB1. However, very few ECRT cases have been published to date, and a systematic characterization of ECRT is missing from the literature. In this study, we report the clinical, pathological, and genomic features of additional cases of ECRT , and show that they are comparable to those of ECRT We also assess whether ECRT , ECRT 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 ECRT display molecular features intermediate between SCCOHT and ECRT ; however, ECRT appear to be more closely related to SCCOHT by DNA methylation. Conversely, both transcriptomics and DNA methylation show a larger gap between SCCOHT and ECRT , potentially supporting their continuous separate classification. Lastly, we show that ECRT display concomitant lack of SMARCA4 (BRG1) and SMARCA2 (BRM) expression at the protein level, similar to what is seen in SCCOHT. Overall, our results expand the knowledge on this rare tumour type and explore the similarities and differences among entities from the 'rhabdoid tumour' spectrum. This article is protected by copyright. All rights reserved.