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

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@article{cffb73b1e7d34b6db5dae66d255abd56,
title = "Nationwide germline whole genome sequencing of 198 consecutive pediatric cancer patients reveals a high incidence of cancer prone syndromes",
abstract = "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.",
author = "Anna Byrjalsen and Hansen, {Thomas V O} and Stoltze, {Ulrik K} and Mehrjouy, {Mana M} and Barnkob, {Nanna Moeller} and Hjalgrim, {Lisa L} and Ren{\'e} Mathiasen and Lautrup, {Charlotte K} and Gregersen, {Pernille A} and Henrik Hasle and Wehner, {Peder S} and Ruta Tuckuviene and Sackett, {Peter Wad} and Laspiur, {Adrian O} and Maria Rossing and Marvig, {Rasmus L} and Niels Tommerup and Olsen, {Tina Elisabeth} and David Scheie and Ramneek Gupta and Anne-Marie Gerdes and Kjeld Schmiegelow and Karin Wadt",
note = "Publisher Copyright: Copyright: {\textcopyright} 2020 Byrjalsen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2020",
month = dec,
day = "17",
doi = "10.1371/JOURNAL.PGEN.1009231",
language = "English",
volume = "16",
pages = "e1009231",
journal = "Plos Genetics",
issn = "1553-7404",
publisher = "Public Library of Science",
number = "12",

}

RIS

TY - JOUR

T1 - Nationwide germline whole genome sequencing of 198 consecutive pediatric cancer patients reveals a high incidence of cancer prone syndromes

AU - Byrjalsen, Anna

AU - Hansen, Thomas V O

AU - Stoltze, Ulrik K

AU - Mehrjouy, Mana M

AU - Barnkob, Nanna Moeller

AU - Hjalgrim, Lisa L

AU - Mathiasen, René

AU - Lautrup, Charlotte K

AU - Gregersen, Pernille A

AU - Hasle, Henrik

AU - Wehner, Peder S

AU - Tuckuviene, Ruta

AU - Sackett, Peter Wad

AU - Laspiur, Adrian O

AU - Rossing, Maria

AU - Marvig, Rasmus L

AU - Tommerup, Niels

AU - Olsen, Tina Elisabeth

AU - Scheie, David

AU - Gupta, Ramneek

AU - Gerdes, Anne-Marie

AU - Schmiegelow, Kjeld

AU - Wadt, Karin

N1 - Publisher Copyright: Copyright: © 2020 Byrjalsen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2020/12/17

Y1 - 2020/12/17

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85098964008&partnerID=8YFLogxK

U2 - 10.1371/JOURNAL.PGEN.1009231

DO - 10.1371/JOURNAL.PGEN.1009231

M3 - Journal article

C2 - 33332384

VL - 16

SP - e1009231

JO - Plos Genetics

JF - Plos Genetics

SN - 1553-7404

IS - 12

M1 - e1009231

ER -

ID: 61712717