[HTML][HTML] Sequencing of DICER1 in sarcomas identifies biallelic somatic DICER1 mutations in an adult-onset embryonal rhabdomyosarcoma
British Journal of Cancer, 2017•nature.com
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 …
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 …
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.
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