Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Identification of Candidate Cancer Predisposing Genes by Whole-Exome Sequencing of Families at High-Risk of Glioma

Ben Kinnersley
* ORCID logo ,
Peter Broderick
,
Daniel Chubb
,
Hanne Bødtcher
,
Karim Labreche
,
Axel de Bernardi
,
Olivier Chinot
,
Christoffer Johansen
,
Marc Sanson
,
Richard Houlston
Version 1 : Received: 23 February 2022 / Approved: 25 February 2022 / Online: 25 February 2022 (09:36:05 CET)

How to cite: Kinnersley, B.; Broderick, P.; Chubb, D.; Bødtcher, H.; Labreche, K.; de Bernardi, A.; Chinot, O.; Johansen, C.; Sanson, M.; Houlston, R. Identification of Candidate Cancer Predisposing Genes by Whole-Exome Sequencing of Families at High-Risk of Glioma. Preprints 2022, 2022020330. https://doi.org/10.20944/preprints202202.0330.v1 Kinnersley, B.; Broderick, P.; Chubb, D.; Bødtcher, H.; Labreche, K.; de Bernardi, A.; Chinot, O.; Johansen, C.; Sanson, M.; Houlston, R. Identification of Candidate Cancer Predisposing Genes by Whole-Exome Sequencing of Families at High-Risk of Glioma. Preprints 2022, 2022020330. https://doi.org/10.20944/preprints202202.0330.v1

Abstract

The genetic aetiology of familial glioma is largely unknown. To gain further insight into the role of rare disruptive variants we performed whole exome sequencing (WES) of 17 glioma families, identifying two families where loss of function mutations in dynein axonemal heavy chain 11 (DNAH11) co-segregated with glioma (DNAH11 p.Ser1470ArgfsTer6 and p.Thr3900Lys) and single families implicating Telomere Replication Complex Component 1 (CTC1 p.Leu1058ProfsTer32) and filamin alpha (FLNA p.Ser1356Phe). We complemented linkage analysis by WES of 150 additional unrelated familial glioma cases and conducting gene burden tests leveraging WES data on 691 cases of glioma from TCGA. Our analysis does not provide support for a hitherto unidentified major cancer gene for glioma but highlights a series of novel candidate predisposition variants/genes, worthy of further investigation to shed light on glioma risk.

Keywords

glioma; genetics; inherited; mutation; germline

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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