Lack of pathogenic germline DICER1 variants in males with testicular germ-cell tumors

Cancer Genet. 2020 Oct;248-249:49-56. doi: 10.1016/j.cancergen.2020.10.002. Epub 2020 Oct 24.


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.

Keywords: DICER1; Exome sequencing; Scrotal ultrasound; Testicular cancer; miRNA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

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


  • Biomarkers, Tumor
  • DICER1 protein, human
  • Ribonuclease III
  • DEAD-box RNA Helicases

Supplementary concepts

  • Testicular Germ Cell Tumor