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

British Journal of Cancer
Leanne de KockW D Foulkes

Abstract

Sarcomas are rare and heterogeneous cancers. We assessed the contribution of DICER1 mutations to sarcoma development. 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. 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. We show that deleterious DICER1 mutations underlie the genetic basis of only a small fraction of sarcomas, in particular ERMS of the urogenital tract.

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Citations

May 16, 2018·Cancers·Jake C RobertsonJulia Thom Oxford
Jul 26, 2019·Human Mutation·Leanne de KockWilliam D Foulkes
Dec 6, 2019·The Journal of Clinical Investigation·Barbara RiveraWilliam D Foulkes
Feb 6, 2020·The American Journal of Surgical Pathology·Vidarshi MuthukumaranaSarah Chiang
Apr 7, 2019·Acta Neuropathologica·Leanne de KockSanda Alexandrescu
Jan 5, 2020·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Leanne de KockWilliam D Foulkes
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Jan 19, 2021·The Journal of Clinical Endocrinology and Metabolism·Anne-Sophie ChongBarbara Rivera
Apr 4, 2021·Biomedicines·Ying-Chin LinJung-Chun Lin
Apr 14, 2021·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Felix K F KommossChristian Koelsche
Oct 7, 2020·International Journal of Gynecological Pathology : Official Journal of the International Society of Gynecological Pathologists·Ju-Yoon YoonW Glenn McCluggage

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Methods Mentioned

BETA
PCR

Software Mentioned

Fluidigm Access Array
PolyPhen2
SIFT

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