TY - JOUR

T1 - Selection criteria for assembling a pediatric cancer predisposition syndrome gene panel

AU - Byrjalsen, Anna

AU - Diets, Illja J.

AU - Bakhuizen, Jette

AU - Hansen, Thomas van Overeem

AU - Schmiegelow, Kjeld

AU - Gerdes, Anne-Marie

AU - Stoltze, Ulrik

AU - Kuiper, Roland P.

AU - Merks, Johannes H. M.

AU - Wadt, Karin

AU - Jongmans, Marjolijn

N1 - Publisher Copyright: © 2021, The Author(s).

PY - 2021

Y1 - 2021

N2 - Increasing use of genomic sequencing enables standardized screening of all childhood cancer predisposition syndromes (CPS) in children with cancer. Gene panels currently used often include adult-onset CPS genes and genes without substantial evidence linking them to cancer predisposition. We have developed criteria to select genes relevant for childhood-onset CPS and assembled a gene panel for use in children with cancer. We applied our criteria to 381 candidate genes, which were selected through two in-house panels (n = 338), a literature search (n = 39), and by assessing two Genomics England’s PanelApp panels (n = 4). We developed evaluation criteria that determined a gene’s eligibility for inclusion on a childhood-onset CPS gene panel. These criteria assessed (1) relevance in childhood cancer by a minimum of five childhood cancer patients reported carrying a pathogenic variant in the gene and (2) evidence supporting a causal relation between variants in this gene and cancer development. 138 genes fulfilled the criteria. In this study we have developed criteria to compile a childhood cancer predisposition gene panel which might ultimately be used in a clinical setting, regardless of the specific type of childhood cancer. This panel will be evaluated in a prospective study. The panel is available on (pediatric-cancer-predisposition-genepanel.nl) and will be regularly updated.

AB - Increasing use of genomic sequencing enables standardized screening of all childhood cancer predisposition syndromes (CPS) in children with cancer. Gene panels currently used often include adult-onset CPS genes and genes without substantial evidence linking them to cancer predisposition. We have developed criteria to select genes relevant for childhood-onset CPS and assembled a gene panel for use in children with cancer. We applied our criteria to 381 candidate genes, which were selected through two in-house panels (n = 338), a literature search (n = 39), and by assessing two Genomics England’s PanelApp panels (n = 4). We developed evaluation criteria that determined a gene’s eligibility for inclusion on a childhood-onset CPS gene panel. These criteria assessed (1) relevance in childhood cancer by a minimum of five childhood cancer patients reported carrying a pathogenic variant in the gene and (2) evidence supporting a causal relation between variants in this gene and cancer development. 138 genes fulfilled the criteria. In this study we have developed criteria to compile a childhood cancer predisposition gene panel which might ultimately be used in a clinical setting, regardless of the specific type of childhood cancer. This panel will be evaluated in a prospective study. The panel is available on (pediatric-cancer-predisposition-genepanel.nl) and will be regularly updated.

KW - Childhood cancer predisposition syndrome

KW - Gene panel

KW - Gene selection

KW - Genetic predisposition

KW - Pediatric cancer

U2 - 10.1007/s10689-021-00254-0

DO - 10.1007/s10689-021-00254-0

M3 - Journal article

C2 - 34061292

AN - SCOPUS:85107376347

VL - 20

SP - 279

EP - 287

JO - Familial Cancer

JF - Familial Cancer

SN - 1389-9600

IS - 4

ER -