Germline Pathogenic <i>DROSHA</i> Variants Are Linked to Pineoblastoma and Wilms Tumor Predisposition
This is the first report of DROSHA-related tumor predisposition. As pineoblastoma and Wilms tumor are also associated with DICER1 GPVs, our results suggest that the tissues of origin for these tumors are uniquely tolerant of general miRNA loss. The miRNA processing-altered 1 pineoblastoma subtype is associated with older age of diagnosis and better outcomes than other subtypes, suggesting DROSHA GPV status may have important clinical and prognostic significance. We suggest that genetic testing for DROSHA GPVs be considered for patients with pineoblastoma, Wilms tumor, or other DICER1-/DGCR8-related conditions and propose surveillance recommendations through research studies for individuals with DROSHA GPVs.
Authors
- Afane Brahimi
- Jo Lynne Rokita (ORCID: https://orcid.org/0000-0003-2171-3627)
- Franck Bourdeaut (ORCID: https://orcid.org/0000-0001-9489-6781)
- Lisa Golmard (ORCID: https://orcid.org/0000-0002-5158-8284)
- Allison Pribnow (ORCID: https://orcid.org/0000-0001-7069-3402)
- Giselle L. Saulnier Sholler (ORCID: https://orcid.org/0000-0002-5599-4757)
- Anita Ng (ORCID: https://orcid.org/0000-0001-8203-667X)
- Rebecca Kaufman (ORCID: https://orcid.org/0000-0001-8535-9730)
- Ryan J. Corbett (ORCID: https://orcid.org/0000-0002-3478-0784)
- Riyue Bao (ORCID: https://orcid.org/0000-0002-6105-1704)
- Joshua David Schiffman (ORCID: https://orcid.org/0000-0002-6968-7694)
- Sharon E. Plon (ORCID: https://orcid.org/0000-0002-9626-0936)
- Hussam Al‐Kateb (ORCID: https://orcid.org/0000-0003-3392-0906)
- Kuan‐lin Huang (ORCID: https://orcid.org/0000-0002-5537-5817)
- Olivier Ingster
- Peter N. Fiorica (ORCID: https://orcid.org/0000-0002-1001-1518)
- D. Williams Parsons (ORCID: https://orcid.org/0000-0002-8775-3501)
- Jeremy S. Haley (ORCID: https://orcid.org/0000-0002-3279-7873)
- Kenneth Chen (ORCID: https://orcid.org/0000-0003-2304-4631)
- Kris Ann P. Schultz (ORCID: https://orcid.org/0000-0002-1788-5832)
- Rose B. McGee (ORCID: https://orcid.org/0000-0001-7392-6515)
- Douglas R. Stewart (ORCID: https://orcid.org/0000-0001-8193-1488)
- Sharon J. Diskin (ORCID: https://orcid.org/0000-0002-7200-8939)
- Angshumoy Roy (ORCID: https://orcid.org/0000-0001-7248-8576)
- Mathilde Filser (ORCID: https://orcid.org/0000-0002-5074-8100)
- Melissa R. Perrino (ORCID: https://orcid.org/0000-0002-0598-7102)
- Julien Masliah‐Planchon (ORCID: https://orcid.org/0000-0002-5596-3926)
- Kenan Onel (ORCID: https://orcid.org/0000-0002-2021-6250)
- David J. Carey (ORCID: https://orcid.org/0000-0001-6404-1950)
- Dominique Stoppa‐Lyonnet (ORCID: https://orcid.org/0000-0002-5438-8309)
- Frank Y. Lin (ORCID: https://orcid.org/0000-0001-6738-844X)
- Jung Kim (ORCID: https://orcid.org/0000-0001-6274-2841)
- Sarah A. Jackson (ORCID: https://orcid.org/0000-0002-9234-7372)
- Jennifer Wong (ORCID: https://orcid.org/0000-0002-1898-6539)
- Sophie Michalak-Provost
- M.S. Sasaki
- Trent Fowler
Institutions
- Roswell Park Comprehensive Cancer Center (US)
- Geisinger Medical Center (US)
- Pennsylvania State University (US)
- St. Jude Children's Research Hospital (US)
- Feinstein Institute for Medical Research (US)
- Mayo Clinic (US)
- Lucile Packard Children's Hospital (US)
- Children's Hospital of Philadelphia (US)
- Children's National (US)
- Inserm (FR)
- University of Pittsburgh (US)
- Palo Alto University (US)
- Baylor College of Medicine (US)
- Université Paris Cité (FR)
- University of Utah (US)
- Université de Lille (FR)
- Université Paris Sciences et Lettres (FR)
- Huntsman Cancer Institute (US)
- WinnMed (US)
- Minnesota West Community & Technical College (US)
- University of Chicago (US)
- Lille’s Cardiology Hospital (FR)
- Sorbonne Paris Cité (FR)
- PEEL Therapeutics (United States) (US)
- Centre Hospitalier Universitaire d'Angers (FR)
- Mayo Clinic in Arizona (US)
- UPMC Hillman Cancer Center (US)
- Children's Minnesota (US)
- University of Pittsburgh Medical Center (US)
- National Cancer Institute (US)
- Mayo Clinic in Florida (US)
- Texas Children's Hospital (US)
- Children's Cancer Center (US)
- Genomic Health (United States) (US)
- Division of Cancer Epidemiology and Genetics
- Université d'Angers (FR)
- Geisinger Health System (US)
- University at Buffalo, State University of New York (US)
- University of Pennsylvania (US)
- Institut Curie (FR)
- Penn State Milton S. Hershey Medical Center (US)
- The University of Texas Southwestern Medical Center (US)
- Stanford University (US)
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- Clinical Cancer Research
- Published
- 2025-02-24
- DOI
- https://doi.org/10.1158/1078-0432.ccr-24-2785
- Citations
- 4
- Primary Topic
- RNA modifications and cancer
- Type
- article
- Field-Weighted Citation Impact
- 3.22