Germline variants in ATM, BRCA2, other cancer predisposition and novel candidate genes are implicated in glioma risk in adult glioma patients with a familial or personal history of tumors
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Familial occurrence of gliomas has been reported in around 5% of patients. Studies on the genetic landscape of glioma predisposition are scarce. Here, leukocyte DNA of 213 adult glioma patients with a familial and/or personal tumor history from 206 families was subjected to whole-exome sequencing. Germline variants (GVs) were analyzed using two approaches: (1) GVs in 164 established cancer predisposition genes (CPGs) or suspected glioma risk genes were extracted and classified; (2) the enrichment of genes with loss-of-function or deleterious missense GVs that were ultrarare or ClinVar likely pathogenic/pathogenic in the glioma versus a control cohort (n = 391) was determined. In 23% (48/213) of glioma patients with a familial/personal tumor history, GVs predicted to be deleterious in CPGs were detected. Of the mutated CPGs, 37% were involved in DNA damage response, including ATM, BRCA2, PMS2, POLE. ATM GVs (n = 6) preferentially predisposed to IDH-mutant astrocytoma (P = 0.007) in patients that were significantly younger at diagnosis than patients without GVs (P = 0.022). BRCA2 GVs (n = 5) were also significantly enriched in glioma patients in approach 2 (P = 0.005). The other mutated CPGs, glioma risk or enriched novel genes play roles in diverse processes, including metabolism and signal transduction. Syn-/metachronous non-brain tumors were diagnosed in 29% of glioma patients with GVs. In 11% of patients, the identified CPG GVs potentially sensitized to targeted therapies, such as PARP, immune checkpoint, or EGFR inhibitors. In conclusion, our study identifies CPGs and novel genes relevant in germline testing of glioma patients with a familial/personal tumor history, possibly resulting in targeted treatment options.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Germline variants in ATM, BRCA2, other cancer predisposition and novel candidate genes are implicated in glioma risk in adult glioma patients with a familial or personal history of tumors
- Date Crossref
- 17/01/2026
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Medizinische Hochschule Hannover pays non établi dans la noticeUniversité ou école supérieure
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Diakovere pays non établi dans la noticeOrganisation à but non lucratif
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Vinzenzkrankenhaus Hannover pays non établi dans la noticeÉtablissement de santé
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Helmholtz Centre for Infection Research pays non établi dans la noticeStructure de recherche
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KRH Klinikum Nordstadt pays non établi dans la noticeÉtablissement de santé
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Asklepios Kliniken Hamburg pays non établi dans la noticeÉtablissement de santé
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Düsseldorf University Hospital pays non établi dans la noticeÉtablissement de santé
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St. Marien-Hospital Bonn pays non établi dans la noticeÉtablissement de santé
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LVR-Klinik Bonn pays non établi dans la noticeÉtablissement de santé
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Heinrich Heine University Düsseldorf pays non établi dans la noticeUniversité ou école supérieure
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International Neuroscience Institute Department of Neurosurgery pays non établi dans la noticeStructure de recherche
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German Cancer Research Center German Cancer Consortium (DKTK) pays non établi dans la noticeStructure de recherche
Medizinische Hochschule Hannover, Diakovere et Vinzenzkrankenhaus Hannover, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.