دورية أكاديمية
Prevalence of (Epi)genetic Predisposing Factors in a 5-Year Unselected National Wilms Tumor Cohort: A Comprehensive Clinical and Genomic Characterization.
| العنوان: | Prevalence of (Epi)genetic Predisposing Factors in a 5-Year Unselected National Wilms Tumor Cohort: A Comprehensive Clinical and Genomic Characterization. |
|---|---|
| المؤلفون: | Hol JA; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands., Kuiper RP; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.; Department of Genetics, University Medical Center Utrecht, Utrecht, the Netherlands., van Dijk F; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands., Waanders E; Department of Genetics, University Medical Center Utrecht, Utrecht, the Netherlands., van Peer SE; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands., Koudijs MJ; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.; Department of Genetics, University Medical Center Utrecht, Utrecht, the Netherlands., Bladergroen R; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands., van Reijmersdal SV; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands., Morgado LM; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands., Bliek J; Department of Clinical Genetics, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., Lombardi MP; Department of Clinical Genetics, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., Hopman S; Department of Genetics, University Medical Center Utrecht, Utrecht, the Netherlands., Drost J; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.; Oncode Institute, Utrecht, the Netherlands., de Krijger RR; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.; Department of Pathology, University Medical Center Utrecht, Utrecht, the Netherlands., van den Heuvel-Eibrink MM; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands., Jongmans MCJ; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.; Department of Genetics, University Medical Center Utrecht, Utrecht, the Netherlands. |
| المصدر: | Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2022 Jun 10; Vol. 40 (17), pp. 1892-1902. Date of Electronic Publication: 2022 Mar 01. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society of Clinical Oncology Country of Publication: United States NLM ID: 8309333 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1527-7755 (Electronic) Linking ISSN: 0732183X NLM ISO Abbreviation: J Clin Oncol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2003- : Alexandria, VA : American Society of Clinical Oncology Original Publication: New York, N.Y. : Grune & Stratton, c1983- |
| مواضيع طبية MeSH: | Beckwith-Wiedemann Syndrome*/diagnosis , Beckwith-Wiedemann Syndrome*/genetics , Beckwith-Wiedemann Syndrome*/pathology , Kidney Neoplasms*/epidemiology , Kidney Neoplasms*/genetics , Kidney Neoplasms*/pathology , Wilms Tumor*/epidemiology , Wilms Tumor*/genetics , Wilms Tumor*/pathology, Adult ; Causality ; Child ; Genetic Predisposition to Disease ; Genomics ; Germ-Line Mutation ; Humans ; Prevalence |
| مستخلص: | Purpose: Wilms tumor (WT) is associated with (epi)genetic predisposing factors affecting a growing number of WT predisposing genes and loci, including those causing Beckwith-Wiedemann spectrum (BWSp) or WT1 -related syndromes. To guide genetic counseling and testing, we need insight into the prevalence of WT predisposing (epi)genetic factors. Patients and Methods: All children diagnosed with WT in the Netherlands between 2015 and 2020 were referred to a clinical geneticist. Phenotypic data, disease characteristics, and diagnostic test results were collected. If no genetic predisposition was identified by targeted diagnostic testing, germline (trio-)whole-exome sequencing and BWSp testing on normal kidney-derived DNA were offered. Results: A total of 126 cases were analyzed of 128 identified patients. (Epi)genetic predisposing factors were present in 42 of 126 patients (33.3%) on the basis of a molecular diagnosis in blood-derived DNA (n = 26), normal kidney-derived DNA (n = 12), or solely a clinical diagnosis of BWSp (n = 4). Constitutional, heterozygous DIS3L2 variants were identified as a recurrent predisposing factor in five patients (4%), with a second somatic hit in 4 of 5 tumors. Twenty patients (16%) were diagnosed with BWSp while four additional patients without BWSp features harbored chromosome 11p15 methylation defects in normal kidney tissue. Remaining findings included WT1 -related syndromes (n = 10), Fanconi anemia (n = 1), neurofibromatosis type 1 (n = 1), and a pathogenic REST variant (n = 1). In addition, (likely) pathogenic variants in adult-onset cancer predisposition genes ( BRCA2 , PMS2 , CHEK2 , and MUTYH ) were identified in 5 of 56 (8.9%) patients with available whole-exome sequencing data. Several candidate WT predisposition genes were identified, which require further validation. Conclusion: (Epi)genetic WT predisposing factors, including mosaic aberrations and recurrent heterozygous DIS3L2 variants, were present in at least 33.3% of patients with WT. On the basis of these results, we encourage standard genetic testing after counseling by a clinical geneticist. Competing Interests: Jarno DrostPatents, Royalties, Other Intellectual Property: WO2016/083613; culture medium for epithelial stem cells and Organoids comprising said stem cells. WO2016/083612; culture medium for expanding breast epithelial stem cellsNo other potential conflicts of interest were reported. |
| التعليقات: | Comment in: J Clin Oncol. 2022 Jun 10;40(17):1853-1860. (PMID: 35500208) |
| References: | Int J Cancer. 2020 Feb 15;146(4):1010-1017. (PMID: 31286500) Nat Genet. 2012 Feb 05;44(3):277-84. (PMID: 22306653) Am J Med Genet A. 2005 Apr 15;134A(2):132-43. (PMID: 15712196) Cancer Cell. 2015 Feb 9;27(2):298-311. (PMID: 25670083) Am J Med Genet. 1998 Oct 2;79(4):268-73. (PMID: 9781906) Eur J Pediatr Surg. 1997 Oct;7(5):308-10. (PMID: 9402494) Int J Cancer. 2019 Aug 15;145(4):941-951. (PMID: 30694527) Eur J Hum Genet. 2019 Feb;27(2):325-330. (PMID: 30291343) Am J Med Genet A. 2008 Oct 1;146A(19):2532-7. (PMID: 18780370) Eur J Hum Genet. 2013 Nov;21(11):1316-9. (PMID: 23486540) Lancet. 2004 Feb 7;363(9407):446-51. (PMID: 14962525) J Med Genet. 2006 Sep;43(9):705-15. (PMID: 16690728) N Engl J Med. 1964 Apr 30;270:922-7. (PMID: 14114111) PLoS Genet. 2018 Jun 18;14(6):e1007399. (PMID: 29912901) Am J Med Genet C Semin Med Genet. 2007 Nov 15;145C(4):357-71. (PMID: 17910077) Clin Cancer Res. 2018 Apr 1;24(7):1594-1603. (PMID: 29351919) Nucleic Acids Res. 2019 Jan 8;47(D1):D941-D947. (PMID: 30371878) Science. 2019 Dec 6;366(6470):1247-1251. (PMID: 31806814) Cancer. 2020 Jul 1;126(13):3114-3121. (PMID: 32320050) Br J Cancer. 2015 Mar 17;112(6):1121-33. (PMID: 25688735) Leukemia. 1993 Jun;7(6):912-5. (PMID: 8388972) Eur J Cancer. 2021 Aug;153:51-63. (PMID: 34134020) Nat Rev Endocrinol. 2018 Apr;14(4):229-249. (PMID: 29377879) N Engl J Med. 2015 Dec 10;373(24):2336-2346. (PMID: 26580448) J Neurosurg Pediatr. 2011 Oct;8(4):353-6. (PMID: 21961578) Pediatr Blood Cancer. 2014 Jan;61(1):140-4. (PMID: 23970395) Eur J Cancer. 2012 Nov;48(17):3249-56. (PMID: 22796116) Nat Genet. 2015 Dec;47(12):1471-4. (PMID: 26551668) Nat Genet. 2017 Oct;49(10):1487-1494. (PMID: 28825729) Nature. 2018 Mar 15;555(7696):321-327. (PMID: 29489754) CA Cancer J Clin. 1981 Nov-Dec;31(6):333-5. (PMID: 6286055) Oncotarget. 2018 Sep 25;9(75):34079-34089. (PMID: 30344923) JAMA Oncol. 2016 May 01;2(5):616-624. (PMID: 26822237) Genes Dev. 2015 Mar 1;29(5):467-82. (PMID: 25737276) Cancer. 1977 Jun;39(6):2550-5. (PMID: 194668) PLoS Genet. 2020 Dec 17;16(12):e1009231. (PMID: 33332384) Eur J Med Genet. 2016 Mar;59(3):116-25. (PMID: 26825391) Nat Commun. 2014 Aug 07;5:4398. (PMID: 25099282) Lancet Child Adolesc Health. 2019 May;3(5):322-331. (PMID: 30885698) N Engl J Med. 2020 Jul 16;383(3):280-282. (PMID: 32668120) Cancer Sci. 2012 Jun;103(6):1129-35. (PMID: 22409817) |
| تواريخ الأحداث: | Date Created: 20220301 Date Completed: 20220609 Latest Revision: 20220926 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC9177240 |
| DOI: | 10.1200/JCO.21.02510 |
| PMID: | 35230882 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1527-7755 |
|---|---|
| DOI: | 10.1200/JCO.21.02510 |