ArticleNature communications2022
The impact of rare germline variants on human somatic mutation processes.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 41 citations in OpenAlex.
- Comprehensive Genomic Analysis of Normal and Cancer Cells Elucidates the Elevated Mutational Burden in Cancer.Cancer research · 2026Article
- A sibling study of variation in parental mutation rates.bioRxiv : the preprint server for biology · 2026Article
- Concurrent Germline-Somatic Alterations and Associations with Cancer Outcomes: A Systematic Review of Concurrent Data Use.Research square · 2026Article
- Genetic landscape of cancer: mechanisms, key genes, and therapeutic implications.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Functional Profiling of DNA Repair Pathways in Lung Cancer Patients Uncovers Radiotherapy-Induced and Cancer-Associated Alterations in Oxidative Lesion Repair.medRxiv : the preprint server for health sciences · 2026Article
- Reconstructing the lifelong history of cells and tissues via somatic mutation analysis.Cellular and molecular life sciences : CMLS · 2025Review
- Variable efficiency of nonsense-mediated mRNA decay across human tissues, tumors and individuals.Genome biology · 2025Article
- Joint inference of mutational signatures from indels and single-nucleotide substitutions reveals prognostic impact of DNA repair deficiencies.Genome medicine · 2025Article
- The Germline and Somatic Origins of Prostate Cancer Heterogeneity.Cancer discovery · 2025Article
- DeBasher: a flow-based programming bash extension for the implementation of complex and interactive workflows with stateful processes.BMC bioinformatics · 2025Article
- Identifying somatic fingerprints of cancers defined by germline and environmental risk factors.Genetic epidemiology · 2024Article
- Mutational signature analyses in multi-child families reveal sources of age-related increases in human germline mutations.Communications biology · 2024Article
- Structure-specific nucleases in genome dynamics and strategies for targeting cancers.Journal of molecular cell biology · 2024Review
- Germline functional variants contribute to somatic mutation and outcomes in neuroblastoma.Nature communications · 2024Article
- Co-expression in tissue-specific gene networks links genes in cancer-susceptibility loci to known somatic driver genes.BMC medical genomics · 2024Article
- Prospective genetic germline evaluation in a consecutive group of adult patients aged <60 years with myelodysplastic syndromes.HemaSphere · 2024Article
- Analysis of 3760 hematologic malignancies reveals rare transcriptomic aberrations of driver genes.Genome medicine · 2024Article
- Assessing the genomic feature of Chinese patients with ampullary adenocarcinoma: potential therapeutic targets.BMC cancer · 2024Article
- Presumed Pathogenic Germ Line and Somatic Variants in African American Thyroid Cancer.Thyroid : official journal of the American Thyroid Association · 2024Article
- Cell cycle gene alterations associate with a redistribution of mutation risk across chromosomal domains in human cancers.Nature cancer · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Somatic mutations are an inevitable component of ageing and the most important cause of cancer. The rates and types of somatic mutation vary across individuals, but relatively few inherited influences on mutation processes are known. We perform a gene-based rare variant association study with diverse mutational processes, using human cancer genomes from over 11,000 individuals of European ancestry. By combining burden and variance tests, we identify 207 associations involving 15 somatic mutational phenotypes and 42 genes that replicated in an independent data set at a false discovery rate of 1%. We associate rare inherited deleterious variants in genes such as MSH3, EXO1, SETD2, and MTOR with two phenotypically different forms of DNA mismatch repair deficiency, and variants in genes such as EXO1, PAXIP1, RIF1, and WRN with deficiency in homologous recombination repair. In addition, we identify associations with other mutational processes, such as APEX1 with APOBEC-signature mutagenesis. Many of the genes interact with each other and with known mutator genes within cellular sub-networks. Considered collectively, damaging variants in the identified genes are prevalent in the population. We suggest that rare germline variation in diverse genes commonly impacts mutational processes in somatic cells.
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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.