Lack of pathogenic germline DICER1 variants in males with testicular germ-cell tumors: DICER1 and testicular cancer
Document Type
Journal Article
Publication Date
10-1-2020
Journal
Cancer Genetics
Volume
248-249
DOI
10.1016/j.cancergen.2020.10.002
Keywords
DICER1; Exome sequencing; miRNA; Scrotal ultrasound; Testicular cancer
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.
APA Citation
Vasta, L., McMaster, M., Harney, L., Ling, A., Kim, J., Harris, A., Carr, A., Damrauer, S., Rader, D., Kember, R., Kanetsky, P., Nathanson, K., Pyle, L., Greene, M., Schultz, K., & Stewart, D. (2020). Lack of pathogenic germline DICER1 variants in males with testicular germ-cell tumors: DICER1 and testicular cancer. Cancer Genetics, 248-249 (). http://dx.doi.org/10.1016/j.cancergen.2020.10.002
