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

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.

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.

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.

Using two complementary approaches, we found no evidence of an association between pathogenic DICER1 variants and TGCT.

Cancer genetics. 2020 Oct 24 [Epub ahead of print]

Lauren M Vasta, Mary L McMaster, Laura A Harney, Alexander Ling, Jung Kim, Anne K Harris, Ann G Carr, Scott M Damrauer, Daniel J Rader, Rachel L Kember, Peter A Kanetsky, Katherine L Nathanson, Louise C Pyle, Mark H Greene, Kris Ann Schultz, Douglas R Stewart, Regeneron Genetics Center (RGC) Research Team

Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, MD, USA; National Capital Consortium, Walter Reed National Military Medical Center, Bethesda, MD, USA., Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, MD, USA; Commissioned Corps of the United States Public Health Service., Westat, Inc, Rockville, MD, USA., Radiology and Imaging Sciences, National Institutes of Health, Bethesda, MD, USA., Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, MD, USA., International Pleuropulmonary Blastoma/DICER1 Registry, Minneapolis, MN, USA., Commissioned Corps of the United States Public Health Service., Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Corporal Michael Crescenz VA Medical Center, Philadelphia, PA, USA., Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA., Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA., Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA., International Pleuropulmonary Blastoma/DICER1 Registry, Minneapolis, MN, USA; Cancer and Blood Disorders, Children's Minnesota, International Pleuropulmonary Blastoma/DICER1 Registry, Minneapolis, MN, USA; International Ovarian and Testicular Stromal Tumor Registry, Children's Minnesota, Minneapolis, MN, USA., Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, MD, USA. Electronic address: .

email news signup