Sequencing of DICER1 in sarcomas identifies biallelic somatic DICER1 mutations in an adult-onset embryonal rhabdomyosarcoma.

Sequencing of DICER1 in sarcomas identifies biallelic somatic DICER1 mutations in an adult-onset embryonal rhabdomyosarcoma.

Br J Cancer. 2017 May 18;116(12):1621-1626

Authors: de Kock L, Rivera B, Revil T, Thorner P, Goudie C, Bouron-Dal Soglio D, Choong CS, Priest JR, van Diest PJ, Tanboon J, Wagner A, Ragoussis J, Choong PF, Foulkes WD

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) 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.British Journal of Cancer advance online publication: 18 May 2017; doi:10.1038/bjc.2017.147 http://ift.tt/2i0JHS9 online 23 May 2017.

PMID: 28524158 [PubMed - as supplied by publisher]

http://ift.tt/2rol7lw