Sequencing of DICER1 in sarcomas identifies biallelic somatic DICER1 mutations in an adult-onset embryonal rhabdomyosarcoma
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) identified in a pleomorphic sarcoma and one germline variant (c.2257-7A>G) may be pathogenic, but the others are considered to be benign.Conclusions:We show that deleterious DICER1 mutations underlie the genetic basis of only a small fraction of sarcomas, in particular ERMS of the urogenital tract.
|Keywords||biallelic, DICER1, embryonal rhabdomyosarcoma, mutations, sarcoma|
|Persistent URL||dx.doi.org/10.1038/bjc.2017.147, hdl.handle.net/1765/100445|
|Journal||British Journal of Cancer|
De Kock, L. (Leanne), Rivera, B. (Barbara), Revil, T. (Timothée), Thorner, P. (Paul), Goudie, C. (Catherine), Bouron-Dal Soglio, D. (Dorothée), … Foulkes, W.D. (2017). Sequencing of DICER1 in sarcomas identifies biallelic somatic DICER1 mutations in an adult-onset embryonal rhabdomyosarcoma. British Journal of Cancer, 116(12), 1621–1626. doi:10.1038/bjc.2017.147