Lack of pathogenic germline DICER1 variants in males with testicular germ-cell tumors.
Ontology highlight
ABSTRACT: Background
Several studies have reported conflicting evidence on the inclusion of testicular germ cell tumors (TGCT) in the DICER1 tumor-predisposition phenotype. We evaluated the relationship between DICER1 and TGCT by reviewing scrotal ultrasounds of males with pathogenic germline variants in DICER1 and queried exome data from TGCT-affected men for DICER1 variants.Methodology
Fifty-four male DICER1-carriers and family controls (n=41) enrolled in the National Cancer Institute (NCI) DICER1 Natural History Study were offered scrotal ultrasounds. These studies were examined by a single radiologist for abnormalities. In parallel, DICER1 variants from two large exome-sequenced TGCT cohorts were extracted. We used previously published AMG-AMP criteria to characterize rare DICER1 variants.Results
There was no observed difference in frequency of testicular cystic structures in DICER1-carriers versus controls. DICER1 variation was not associated with TGCT in the NCI DICER1-carriers. In 1,264 exome-sequenced men with TGCT, none harbored ClinVar- or InterVar-determined pathogenic or likely pathogenic variants in DICER1. Three DICER1 variants of uncertain significance (one case and two controls) were predicted "damaging" based on a priori criteria.Conclusion
Using two complementary approaches, we found no evidence of an association between pathogenic DICER1 variants and TGCT.
SUBMITTER: Vasta LM
PROVIDER: S-EPMC7704203 | biostudies-literature | 2020 Oct
REPOSITORIES: biostudies-literature
Publications
Lack of pathogenic germline DICER1 variants in males with testicular germ-cell tumors.
Vasta Lauren M LM McMaster Mary L ML Harney Laura A LA Ling Alexander A Kim Jung J Harris Anne K AK Carr Ann G AG Damrauer Scott M SM Rader Daniel J DJ Kember Rachel L RL Kanetsky Peter A PA Nathanson Katherine L KL Pyle Louise C LC Greene Mark H MH Schultz Kris Ann KA Stewart Douglas R DR
Cancer genetics 20201024
<h4>Background</h4>Several studies have reported conflicting evidence on the inclusion of testicular germ cell tumors (TGCT) in the DICER1 tumor-predisposition phenotype. We evaluated the relationship between DICER1 and TGCT by reviewing scrotal ultrasounds of males with pathogenic germline variants in DICER1 and queried exome data from TGCT-affected men for DICER1 variants.<h4>Methodology</h4>Fifty-four male DICER1-carriers and family controls (n=41) enrolled in the National Cancer Institute (N ...[more]
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