Title: Lack of pathogenic germline DICER1 variants in males with testicular germ-cell tumors.
Authors: Vasta, Lauren M; McMaster, Mary L; Harney, Laura A; Ling, Alexander; Kim, Jung; Harris, Anne K; Carr, Ann G; Damrauer, Scott M; Rader, Daniel J; Kember, Rachel L; Kanetsky, Peter A; Nathanson, Katherine L; Pyle, Louise C; Greene, Mark H; Schultz, Kris Ann; Stewart, Douglas R; Regeneron Genetics Center (RGC) Research Team
Published In Cancer Genet, (2020 10)
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.
PubMed ID: 33158809
MeSH Terms: Adolescent; Adult; Aged; Biomarkers, Tumor/genetics*; Case-Control Studies; Child; Child, Preschool; DEAD-box RNA Helicases/genetics*; Female; Genetic Predisposition to Disease*; Genotype; Germ-Line Mutation*; Humans; Infant; Infant, Newborn; Male; Middle Aged; Neoplasms, Germ Cell and Embryonal/genetics*; Neoplasms, Germ Cell and Embryonal/pathology*; Prognosis; Ribonuclease III/genetics*; Testicular Neoplasms/genetics*; Testicular Neoplasms/pathology*; Young Adult