Genome-wide analysis of high-risk primary brain cancer pedigrees identifies PDXDC1 as a candidate brain cancer predisposition gene.
PDXDC1
UPDB
linkage analysis
primary brain cancer
Journal
Neuro-oncology
ISSN: 1523-5866
Titre abrégé: Neuro Oncol
Pays: England
ID NLM: 100887420
Informations de publication
Date de publication:
25 02 2021
25 02 2021
Historique:
pubmed:
10
7
2020
medline:
28
4
2021
entrez:
10
7
2020
Statut:
ppublish
Résumé
There is evidence for an inherited contribution to primary brain cancer. Linkage analysis of high-risk brain cancer pedigrees has identified candidate regions of interest in which brain cancer predisposition genes are likely to reside. Genome-wide linkage analysis was performed in a unique set of 11 informative, extended, high-risk primary brain cancer pedigrees identified in a population genealogy database, which include from 2 to 6 sampled, related primary brain cancer cases. Access to formalin-fixed paraffin embedded tissue samples archived in a biorepository allowed analysis of extended pedigrees. Individual high-risk pedigrees were singly informative for linkage at multiple regions. Suggestive evidence for linkage was observed on chromosomes 2, 3, 14, and 16. The chromosome 16 region in particular contains a promising candidate gene, pyridoxal-dependent decarboxylase domain-containing 1 (PDXDC1), with prior evidence for involvement with glioblastoma from other previously reported experimental settings, and contains the lead single nucleotide polymorphism (rs3198697) from the linkage analysis of the chromosome 16 region. Pedigrees with a statistical excess of primary brain cancers have been identified in a unique genealogy resource representing the homogeneous Utah population. Genome-wide linkage analysis of these pedigrees has identified a potential candidate predisposition gene, as well as multiple candidate regions that could harbor predisposition loci, and for which further analysis is suggested.
Sections du résumé
BACKGROUND
There is evidence for an inherited contribution to primary brain cancer. Linkage analysis of high-risk brain cancer pedigrees has identified candidate regions of interest in which brain cancer predisposition genes are likely to reside.
METHODS
Genome-wide linkage analysis was performed in a unique set of 11 informative, extended, high-risk primary brain cancer pedigrees identified in a population genealogy database, which include from 2 to 6 sampled, related primary brain cancer cases. Access to formalin-fixed paraffin embedded tissue samples archived in a biorepository allowed analysis of extended pedigrees.
RESULTS
Individual high-risk pedigrees were singly informative for linkage at multiple regions. Suggestive evidence for linkage was observed on chromosomes 2, 3, 14, and 16. The chromosome 16 region in particular contains a promising candidate gene, pyridoxal-dependent decarboxylase domain-containing 1 (PDXDC1), with prior evidence for involvement with glioblastoma from other previously reported experimental settings, and contains the lead single nucleotide polymorphism (rs3198697) from the linkage analysis of the chromosome 16 region.
CONCLUSIONS
Pedigrees with a statistical excess of primary brain cancers have been identified in a unique genealogy resource representing the homogeneous Utah population. Genome-wide linkage analysis of these pedigrees has identified a potential candidate predisposition gene, as well as multiple candidate regions that could harbor predisposition loci, and for which further analysis is suggested.
Identifiants
pubmed: 32644145
pii: 5869416
doi: 10.1093/neuonc/noaa161
pmc: PMC7906047
doi:
Substances chimiques
Pyridoxal
3THM379K8A
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
277-283Subventions
Organisme : NCATS NIH HHS
ID : UL1 TR002538
Pays : United States
Informations de copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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