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Nationwide germline whole genome sequencing of 198 consecutive pediatric cancer patients reveals a high incidence of cancer prone syndromes.

التفاصيل البيبلوغرافية
العنوان: Nationwide germline whole genome sequencing of 198 consecutive pediatric cancer patients reveals a high incidence of cancer prone syndromes.
المؤلفون: Byrjalsen A; Department of Clinical Genetics, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.; Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark., Hansen TVO; Department of Clinical Genetics, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.; Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark., Stoltze UK; Department of Clinical Genetics, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark., Mehrjouy MM; Department of Clinical Genetics, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.; Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark., Barnkob NM; Department of Health Technology, Technical University of Denmark, Copenhagen, Denmark., Hjalgrim LL; Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark., Mathiasen R; Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark., Lautrup CK; Department of Clinical Genetics, Aalborg University Hospital, Aalborg, Denmark., Gregersen PA; Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark., Hasle H; Department of Paediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark., Wehner PS; Department of Paediatric Hematology and Oncology, H. C. Andersen Children's Hospital, Odense University Hospital, Odense, Denmark., Tuckuviene R; Department of Paediatrics and Adolescent Medicine, Aalborg University Hospital, Aalborg, Denmark., Sackett PW; Department of Health Technology, Technical University of Denmark, Copenhagen, Denmark., Laspiur AO; Department of Health Technology, Technical University of Denmark, Copenhagen, Denmark., Rossing M; Center for Genomic Medicine, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark., Marvig RL; Center for Genomic Medicine, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark., Tommerup N; Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark., Olsen TE; Department of Pathology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark., Scheie D; Department of Pathology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark., Gupta R; Department of Health Technology, Technical University of Denmark, Copenhagen, Denmark., Gerdes AM; Department of Clinical Genetics, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark., Schmiegelow K; Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.; Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Wadt K; Department of Clinical Genetics, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
المصدر: PLoS genetics [PLoS Genet] 2020 Dec 17; Vol. 16 (12), pp. e1009231. Date of Electronic Publication: 2020 Dec 17 (Print Publication: 2020).
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101239074 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7404 (Electronic) Linking ISSN: 15537390 NLM ISO Abbreviation: PLoS Genet Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science, c2005-
مواضيع طبية MeSH: Germ-Line Mutation*, Genetic Testing/*statistics & numerical data , Neoplastic Syndromes, Hereditary/*epidemiology , Whole Genome Sequencing/*statistics & numerical data, Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Incidence ; Infant ; Male ; Mutation Rate ; Neoplastic Syndromes, Hereditary/genetics
مستخلص: Purpose: Historically, cancer predisposition syndromes (CPSs) were rarely established for children with cancer. This nationwide, population-based study investigated how frequently children with cancer had or were likely to have a CPS.
Methods: Children (0-17 years) in Denmark with newly diagnosed cancer were invited to participate in whole-genome sequencing of germline DNA. Suspicion of CPS was assessed according to Jongmans'/McGill Interactive Pediatric OncoGenetic Guidelines (MIPOGG) criteria and familial cancer diagnoses were verified using population-based registries.
Results: 198 of 235 (84.3%) eligible patients participated, of whom 94/198 (47.5%) carried pathogenic variants (PVs) in a CPS gene or had clinical features indicating CPS. Twenty-nine of 198 (14.6%) patients harbored a CPS, of whom 21/198 (10.6%) harbored a childhood-onset and 9/198 (4.5%) an adult-onset CPS. In addition, 23/198 (11.6%) patients carried a PV associated with biallelic CPS. Seven of the 54 (12.9%) patients carried two or more variants in different CPS genes. Seventy of 198 (35.4%) patients fulfilled the Jongmans' and/or MIPOGG criteria indicating an underlying CPS, including two of the 9 (22.2%) patients with an adult-onset CPS versus 18 of the 21 (85.7%) patients with a childhood-onset CPS (p = 0.0022), eight of the additional 23 (34.8%) patients with a heterozygous PV associated with biallelic CPS, and 42 patients without PVs. Children with a central nervous system (CNS) tumor had family members with CNS tumors more frequently than patients with other cancers (11/44, p = 0.04), but 42 of 44 (95.5%) cases did not have a PV in a CPS gene.
Conclusion: These results demonstrate the value of systematically screening pediatric cancer patients for CPSs and indicate that a higher proportion of childhood cancers may be linked to predisposing germline variants than previously supposed.
Competing Interests: The authors have declared that no competing interests exist.
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تواريخ الأحداث: Date Created: 20201217 Date Completed: 20210121 Latest Revision: 20210121
رمز التحديث: 20240829
مُعرف محوري في PubMed: PMC7787686
DOI: 10.1371/journal.pgen.1009231
PMID: 33332384
قاعدة البيانات: MEDLINE
الوصف
تدمد:1553-7404
DOI:10.1371/journal.pgen.1009231