ArticleScientific reports2021
A computational and structural analysis of germline and somatic variants affecting the DDR mechanism, and their impact on human diseases.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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6 citing papers in PubMed, 6 citations in OpenAlex.
- Feasibility of long-read sequencing to identify molecular alterations in an Indonesian cohort of locally advanced to advanced nasopharyngeal cancer.Scientific reports · 2025Article
- Heterozygous mutation in BRCA2 induces accelerated age-dependent decline in sperm quality with male subfertility in rats.Scientific reports · 2025Article
- Survey and improvement strategies for gene prioritization with large language models.Bioinformatics advances · 2025Article
- Methylation-Driven Gene PLAU as a Potential Prognostic Marker for Differential Thyroid Carcinoma.Frontiers in cell and developmental biology · 2022Article
- An integrated somatic and germline approach to aid interpretation of germline variants of uncertain significance in cancer susceptibility genes.Frontiers in oncology · 2022Article
- Systematic Analysis of FASTK Gene Family Alterations in Cancer.International journal of molecular sciences · 2021Article
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Authors and funding
4 authors at 2 institutions in 3 countries.
Funding
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Abstract
DNA-Damage Response (DDR) proteins are crucial for maintaining the integrity of the genome by identifying and repairing errors in DNA. Variants affecting their function can have severe consequences since failure to repair damaged DNA can result in cells turning cancerous. Here, we compare germline and somatic variants in DDR genes, specifically looking at their locations in the corresponding three-dimensional (3D) structures, Pfam domains, and protein-protein interaction interfaces. We show that somatic variants in metastatic cases are more likely to be found in Pfam domains and protein interaction interfaces than are pathogenic germline variants or variants of unknown significance (VUS). We also show that there are hotspots in the structures of ATM and BRCA2 proteins where pathogenic germline, and recurrent somatic variants from primary and metastatic tumours, cluster together in 3D. Moreover, in the ATM, BRCA1 and BRCA2 genes from prostate cancer patients, the distributions of germline benign, pathogenic, VUS, and recurrent somatic variants differ across Pfam domains. Together, these results provide a better characterisation of the most recurrent affected regions in DDRs and could help in the understanding of individual susceptibility to tumour development.
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