Matches in SemOpenAlex for { <https://semopenalex.org/work/W3171719783> ?p ?o ?g. }
Showing items 1 to 81 of
81
with 100 items per page.
- W3171719783 endingPage "i40" @default.
- W3171719783 startingPage "i39" @default.
- W3171719783 abstract "Abstract Germline variants are known to contribute to the pathogenesis of specific central nervous system (CNS) tumor subtypes; however, a large pan-pediatric brain and nervous system cancer germline susceptibility study has not been performed. To define the prevalence and spectrum of pathogenic variants in known cancer predisposition genes (CPGs; n=200), we analyzed whole genome sequencing (WGS) data from 880 pediatric subjects across 19 different cancer types in the Children’s Brain Tumor Network (CTBN). Data were aligned using BWA. Variants were called using GATK and annotated with SnpEff and ANNOVAR. After quality control, variants with a minor allele frequency (MAF) < 0.1% in Gnomad 2.11 or ExAC were retained. Pathogenicity was assessed with American College of Medical Genetics (ACMG) guidelines using a lab-developed modification of ClinVar and InterVar. Automated pathogenic/likely pathogenic (P-LP) calls were manually reviewed by two cancer predisposition clinicians and a bioinformatician. Frequency of P-LP variants was assessed and gene burden testing was performed against Gnomad3.1 (without cancer samples) using Fisher’s exact test with Bonferroni adjustment. We observed 214 P-LP variants involving 190 unique individuals (21.6% of cohort). As expected, the most frequent variants were observed in NF1, NF2, and TP53(n=40 variants in 21% of individuals). ATM, TSC2 and CHEK2 variants (n=23) were observed in another 12% of individuals. An increased burden of P-LP variants was observed for 5 of these 6 genes (p = 1.7x10-25 to 1.4x10-2, CHEK2 p=5.5x10-2). We also identified 5 variants in BRCA2 (3 in high-grade glioma), 7 in REQC helicases (BLM, WRN, REQL4), and 16 variants in Fanconi anemia genes. Overall, cases harbored increased burden in P-LP variants in CPG genes (p=8.8x-18) and the subset of DNA repair genes (p=4.7x10-4). In conclusion we confirmed the association of variants in established predisposition genes while potentially identifying novel variants and genes associated in CNS tumors." @default.
- W3171719783 created "2021-06-22" @default.
- W3171719783 creator A5005796905 @default.
- W3171719783 creator A5012955659 @default.
- W3171719783 creator A5015199029 @default.
- W3171719783 creator A5028450298 @default.
- W3171719783 creator A5037123158 @default.
- W3171719783 creator A5041067471 @default.
- W3171719783 creator A5058890056 @default.
- W3171719783 creator A5064372210 @default.
- W3171719783 creator A5078757901 @default.
- W3171719783 date "2021-06-01" @default.
- W3171719783 modified "2023-10-14" @default.
- W3171719783 title "OMIC-12. PREVALENCE AND SPECTRUM OF GERMLINE PATHOGENIC VARIANTS IN CANCER PREDISPOSITION GENES ACROSS THE CHILDREN’S BRAIN TUMOR NETWORK (CBTN)" @default.
- W3171719783 doi "https://doi.org/10.1093/neuonc/noab090.159" @default.
- W3171719783 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8168125" @default.
- W3171719783 hasPublicationYear "2021" @default.
- W3171719783 type Work @default.
- W3171719783 sameAs 3171719783 @default.
- W3171719783 citedByCount "0" @default.
- W3171719783 crossrefType "journal-article" @default.
- W3171719783 hasAuthorship W3171719783A5005796905 @default.
- W3171719783 hasAuthorship W3171719783A5012955659 @default.
- W3171719783 hasAuthorship W3171719783A5015199029 @default.
- W3171719783 hasAuthorship W3171719783A5028450298 @default.
- W3171719783 hasAuthorship W3171719783A5037123158 @default.
- W3171719783 hasAuthorship W3171719783A5041067471 @default.
- W3171719783 hasAuthorship W3171719783A5058890056 @default.
- W3171719783 hasAuthorship W3171719783A5064372210 @default.
- W3171719783 hasAuthorship W3171719783A5078757901 @default.
- W3171719783 hasBestOaLocation W31717197831 @default.
- W3171719783 hasConcept C104317684 @default.
- W3171719783 hasConcept C109825262 @default.
- W3171719783 hasConcept C121608353 @default.
- W3171719783 hasConcept C13514818 @default.
- W3171719783 hasConcept C157410074 @default.
- W3171719783 hasConcept C180754005 @default.
- W3171719783 hasConcept C2776071976 @default.
- W3171719783 hasConcept C2778144015 @default.
- W3171719783 hasConcept C37463918 @default.
- W3171719783 hasConcept C501734568 @default.
- W3171719783 hasConcept C54355233 @default.
- W3171719783 hasConcept C64474127 @default.
- W3171719783 hasConcept C67636389 @default.
- W3171719783 hasConcept C86803240 @default.
- W3171719783 hasConceptScore W3171719783C104317684 @default.
- W3171719783 hasConceptScore W3171719783C109825262 @default.
- W3171719783 hasConceptScore W3171719783C121608353 @default.
- W3171719783 hasConceptScore W3171719783C13514818 @default.
- W3171719783 hasConceptScore W3171719783C157410074 @default.
- W3171719783 hasConceptScore W3171719783C180754005 @default.
- W3171719783 hasConceptScore W3171719783C2776071976 @default.
- W3171719783 hasConceptScore W3171719783C2778144015 @default.
- W3171719783 hasConceptScore W3171719783C37463918 @default.
- W3171719783 hasConceptScore W3171719783C501734568 @default.
- W3171719783 hasConceptScore W3171719783C54355233 @default.
- W3171719783 hasConceptScore W3171719783C64474127 @default.
- W3171719783 hasConceptScore W3171719783C67636389 @default.
- W3171719783 hasConceptScore W3171719783C86803240 @default.
- W3171719783 hasIssue "Supplement_1" @default.
- W3171719783 hasLocation W31717197831 @default.
- W3171719783 hasLocation W31717197832 @default.
- W3171719783 hasOpenAccess W3171719783 @default.
- W3171719783 hasPrimaryLocation W31717197831 @default.
- W3171719783 hasRelatedWork W17174532 @default.
- W3171719783 hasRelatedWork W20372389 @default.
- W3171719783 hasRelatedWork W23497526 @default.
- W3171719783 hasRelatedWork W25049655 @default.
- W3171719783 hasRelatedWork W29693034 @default.
- W3171719783 hasRelatedWork W29894752 @default.
- W3171719783 hasRelatedWork W31614829 @default.
- W3171719783 hasRelatedWork W33050379 @default.
- W3171719783 hasRelatedWork W3720132 @default.
- W3171719783 hasRelatedWork W39863934 @default.
- W3171719783 hasVolume "23" @default.
- W3171719783 isParatext "false" @default.
- W3171719783 isRetracted "false" @default.
- W3171719783 magId "3171719783" @default.
- W3171719783 workType "article" @default.