| Title: |
Wilms tumor characteristics in children with heterozygous germline DIS3L2 variants |
| Authors: |
van Peer, S.E.; Treger, T.D.; Wegert, J.; Hol, J.A.; Le Gall, J.; Jakkula, E.E.; Kamihara, J.; Mullen, E.A.; Graf, N.; Behjati, S.; Al-Saadi, R.; Duncan, C.; Schienda, J.; de Putter, Robin; Brzezinski, J.; Verschuur, A.; Michaeli, O.; Ortiz, M.V.; Herkert, J.C.; Armstrong, R.; Waanders, E.; Kuiper, R.P.; van den Heuvel-Eibrink, M.M.; Gessler, M.; Jongmans, M.C.J. |
| Source: |
GENETICS IN MEDICINE ; ISSN: 1098-3600 ; ISSN: 1530-0366 |
| Publication Year: |
2025 |
| Collection: |
Ghent University Academic Bibliography |
| Subject Terms: |
Medicine and Health Sciences; Biology and Life Sciences; Cancer predisposition; Nephroblastoma; Pediatric; Wilms tumor; AT-RISK CHILDREN; PERLMAN SYNDROME; MUTATIONS; GAIN; 1Q; RECOMMENDATIONS; SURVEILLANCE; ASSOCIATION; OVERGROWTH |
| Description: |
Purpose: Heterozygous germline DIS3L2 pathogenic variants were recently linked to Wilms tumor (WT) predisposition. Limited data on cancer penetrance and characteristics complicate surveillance/management recommendations. This study aims to describe an extended cohort of children with WTs and heterozygous germline DIS3L2 (likely) pathogenic variants ([L]PVs). Methods: Clinical and tumor data of children with WT and heterozygous germline DIS3L2 (L) PVs were retrospectively collected. Results: Thirty-four children were identified, including 4 familial cases. Germline (L)PVs included exon 9 deletions (n = 28) and other (n = 6) (L)PVs. Seventeen parents were confirmed to have the DIS3L2 (L)PV, of whom 1 had a past WT. Median age at WT diagnosis was 41 months (range: 8-101). A somatic second hit in DIS3L2 was found in 19 of 20 children with genetic tumor data. Five children had bilateral WTs and 11 had metastases (32%). Eight children had high-risk tumor histology (24%, of which 7 post-chemotherapy blastemal). Three children relapsed or developed a second primary tumor; 4 children were deceased. Recurring clinical features were lacking. Conclusion: Children with WTs and heterozygous germline DIS3L2 (L)PVs lack a recognizable phenotype. DIS3L2 (L)PVs are a cause for familial WT, but WT penetrance is likely low. This cohort exhibits a high percentage of metastases and high-risk blastemal tumors, which need further study. (c) 2025 The Authors. Published by Elsevier Inc. on behalf of American College of Medical Genetics and Genomics. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
https://biblio.ugent.be/publication/01KG4KBCMWYK8QW1KDTJDB2E0W; https://doi.org/10.1016/j.gim.2025.101478; https://biblio.ugent.be/publication/01KG4KBCMWYK8QW1KDTJDB2E0W/file/01KGF7YEV7V7FP4NY3RFGS8MFR |
| DOI: |
10.1016/j.gim.2025.101478 |
| Availability: |
https://biblio.ugent.be/publication/01KG4KBCMWYK8QW1KDTJDB2E0W; https://hdl.handle.net/1854/LU-01KG4KBCMWYK8QW1KDTJDB2E0W; https://doi.org/10.1016/j.gim.2025.101478; https://biblio.ugent.be/publication/01KG4KBCMWYK8QW1KDTJDB2E0W/file/01KGF7YEV7V7FP4NY3RFGS8MFR |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.E60CEBDC |
| Database: |
BASE |