학술논문
Nationwide germline whole genome sequencing of 198 consecutive pediatric cancer patients reveals a high incidence of cancer prone syndromes.
Document Type
article
Author
Anna Byrjalsen; Thomas V O Hansen; Ulrik K Stoltze; Mana M Mehrjouy; Nanna Moeller Barnkob; Lisa L Hjalgrim; René Mathiasen; Charlotte K Lautrup; Pernille A Gregersen; Henrik Hasle; Peder S Wehner; Ruta Tuckuviene; Peter Wad Sackett; Adrian O Laspiur; Maria Rossing; Rasmus L Marvig; Niels Tommerup; Tina Elisabeth Olsen; David Scheie; Ramneek Gupta; Anne-Marie Gerdes; Kjeld Schmiegelow; Karin Wadt
Source
PLoS Genetics, Vol 16, Iss 12, p e1009231 (2020)
Subject
Language
English
ISSN
1553-7390
1553-7404
1553-7404
Abstract
PurposeHistorically, 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.MethodsChildren (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.Results198 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.ConclusionThese 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.