Evidence map›Paper›PMID 41546701›Full record

ArticleActa neuropathologica2026

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.

Frank Brand, Lily S Rose, Amir H Akbarzadeh, Christine A M Weber, Isabel Eckert, Gunnar Schmidt, Bernd Auber, Alisa Förster, Ulrike Beyer, Robert Geffers and 15 more

Abstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Acta neuropathologica, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

25 authors.

Frank Brand *Department of Human Genetics, Hannover Medical School, OE 6300, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
Lily S Rose *Department of Human Genetics, Hannover Medical School, OE 6300, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
Amir H AkbarzadehDepartment of Human Genetics, Hannover Medical School, OE 6300, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
Christine A M WeberDepartment of Human Genetics, Hannover Medical School, OE 6300, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
Isabel EckertDepartment of Neurology, Henriettenstift, Diakovere Krankenhaus gGmbH, Hannover, Germany.
Gunnar SchmidtDepartment of Human Genetics, Hannover Medical School, OE 6300, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
Bernd AuberDepartment of Human Genetics, Hannover Medical School, OE 6300, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
Alisa FörsterDepartment of Human Genetics, Hannover Medical School, OE 6300, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
Ulrike BeyerDepartment of Human Genetics, Hannover Medical School, OE 6300, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
Robert GeffersGenome Analytics Research Group, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Stephan BartelsInstitute of Pathology, Hannover Medical School, Hannover, Germany.
Michael LalkDepartment of Neurosurgery, KRH Klinikum Nordstadt, Hannover, Germany.
Manolis PolemikosDepartment of Neurosurgery, Hannover Medical School, Hannover, Germany.
Michael FrieseDepartment of Pathology and Neuropathology, Asklepios Klinik Nord-Heidberg, Hamburg, Germany.
Michael SabelDepartment of Neurosurgery, University Hospital Düsseldorf and Heinrich Heine University, Medical Faculty, Düsseldorf, Germany.
Philipp SchwenkenbecherDepartment of Neurology, Hannover Medical School, Hannover, Germany.
Paul KremerDepartment of Neurosurgery, Asklepios Klinik Nord-Heidberg, Hamburg, Germany.
Arya NabaviDepartment of Neurosurgery, KRH Klinikum Nordstadt, Hannover, Germany.
Amir SamiiDepartment of Neurosurgery, International Neuroscience Institute, Hannover, Germany.
Ulrich LehmannInstitute of Pathology, Hannover Medical School, Hannover, Germany.
Guido ReifenbergerInstitute of Neuropathology, University Hospital Düsseldorf and Heinrich Heine University, Medical Faculty, Düsseldorf, Germany.
Joachim K KraussDepartment of Neurosurgery, Hannover Medical School, Hannover, Germany.
Bettina WieseDepartment of Neurology, Henriettenstift, Diakovere Krankenhaus gGmbH, Hannover, Germany.
Christian HartmannDepartment of Neuropathology, Institute of Pathology, Hannover Medical School, Hannover, Germany.
Ruthild G WeberDepartment of Human Genetics, Hannover Medical School, OE 6300, Carl-Neuberg-Str. 1, 30625, Hannover, Germany. Weber.Ruthild@mh-hannover.de.

Funding

Wilhelm Sander-Stiftung 2018.097.1
6 · The paper itself

Abstract

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.

Indexed as

Brain NeoplasmsGenetic Predisposition to DiseaseGerm-Line MutationGliomaAtaxia Telangiectasia Mutated ProteinsBRCA2 ProteinCase-Control StudiesDNA Polymerase IIExome SequencingFemaleGenetic Risk ScoreGermanyHumansMaleMiddle AgedMismatch Repair Endonuclease PMS2Ataxia Telangiectasia Mutated ProteinsATM protein, humanBRCA2 ProteinBRCA2 protein, humanDNA Polymerase IIMismatch Repair Endonuclease PMS2PMS2 protein, humanPOLE protein, humanPoly-ADP-Ribose Binding ProteinsAdult-type diffuse gliomaATMBRCA2Cancer predisposition genesGermline variants

Identifiers

PMID41546701
PMCPMC12812103

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.