Related Experiment Video
Updated: Aug 6, 2025
08:01
Generation and Expansion of Primary, Malignant Pleural Mesothelioma Tumor Lines
Published on: April 21, 2022
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New pathogenic germline variants identified in mesothelioma
Laila Belcaid1, Birgitte Bertelsen2, Karin Wadt3
1Dept. of Oncology, Copenhagen University Hospital, Rigshospitalet, Denmark.
Lung Cancer (Amsterdam, Netherlands)
|March 21, 2023
Summary
Germline pathogenic variants (PVs) are common in mesothelioma patients, particularly in DNA repair genes. This suggests germline testing is valuable for identifying potential therapeutic targets and for genetic counseling in mesothelioma.
Area of Science:
- Oncology
- Genetics
- Cancer Research
Background:
- Mesothelioma is linked to asbestos, exhibits tumor heterogeneity, and aggressive behavior.
- Identifying germline pathogenic variants (PVs) in mesothelioma is crucial for discovering actionable targets and for genetic counseling.
Purpose of the Study:
- To investigate the frequency and spectrum of germline PVs in mesothelioma patients.
- To identify potential actionable therapeutic targets and understand the role of DNA repair pathways in mesothelioma.
Main Methods:
- Whole exome sequencing (WES) or whole genome sequencing (WGS) was performed on 44 mesothelioma patients.
- Germline variants were filtered using a 168-gene panel associated with inherited cancer and classified per ACMG/AMP guidelines.
Main Results:
- 36% of patients carried pathogenic or likely pathogenic variants in 13 cancer-associated genes.
- Germline PVs were predominantly found in DNA repair pathways, notably homologous recombination repair (HRR) (75%).
- Germline variants in NBN and RAD51B, not previously linked to mesothelioma, were identified.
Conclusions:
- A high frequency of germline PVs exists in mesothelioma patients.
- Germline testing is supported in mesothelioma, with the HRR pathway showing promise as an actionable target.
- New genetic associations (NBN, RAD51B) for mesothelioma were identified, warranting further investigation.
Keywords:
Cancer geneticsGermline variantsHomologous recombination pathwayMesotheliomaPrecision oncologyMore Related Videos
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