Journal article
Sequencing of DICER1 in sarcomas identifies biallelic somatic DICER1 mutations in an adult-onset embryonal rhabdomyosarcoma
L De Kock, B Rivera, T Revil, P Thorner, C Goudie, D Bouron-Dal Soglio, CS Choong, JR Priest, PJ Van Diest, J Tanboon, A Wagner, J Ragoussis, PFM Choong, WD Foulkes
British Journal of Cancer | NATURE PUBLISHING GROUP | Published : 2017
DOI: 10.1038/bjc.2017.147
Abstract
Background:Sarcomas are rare and heterogeneous cancers. We assessed the contribution of DICER1 mutations to sarcoma development.Methods:The coding region of DICER1 was sequenced in 67 sarcomas using a custom Fluidigm Access Array. The RNase III domains were Sanger sequenced in six additional sarcomas to identify hotspot DICER1 variants.Results:The median age of sarcoma diagnosis was 45.7 years (range: 3 months to 87.4 years). A recurrent embryonal rhabdomyosarcoma (ERMS) of the broad ligament, first diagnosed at age 23 years, harboured biallelic pathogenic somatic DICER1 variants (1 truncating and 1 RNase IIIb missense). We identified nine other DICER1 variants. One somatic variant (p.L1070V..
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Funding Acknowledgements
We thank the patients for their participation in the study, Ms Leanne Taylor, Ms Brooke Backman, and Mr HJ Dubbink for providing pathology material, and Dr Leon van Kempen, Dr George Chong, and Karin Delorme of the Molecular Diagnostics Laboratory, Jewish General Hospital, for assistance with the TruSight Tumor 15 capture and sequencing of case 1. We also thank Nelly Sabbaghian for assistance with the MLPA assay, and Dr Tara Paton and Guillermo Casallo of The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Canada, for assistance with the ddPCR experiments. A portion of biospecimens and data used in this research were obtained from the Victorian Cancer Biobank, Victoria, Australia, with appropriate ethics approval. The Victorian Cancer Biobank is supported by the Victorian Government. This work was supported by Alex's Lemonade Stand Foundation and by C<SUP>17</SUP>, the latter with funding from Childhood Cancer Canada Foundation (to WDF), the Vanier Canada Graduate Scholarship (to LdK), and the Kate McGarrigle Fellowship in Sarcoma Research of the Cedars Cancer Centre (to BR).