{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T11:43:45Z","timestamp":1753875825476,"version":"3.41.2"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:00:00Z","timestamp":1709251200000},"content-version":"vor","delay-in-days":39,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CityU Strategic Interdisciplinary Research Grant","award":["9043559"],"award-info":[{"award-number":["9043559"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32270690","32070671"],"award-info":[{"award-number":["32270690","32070671"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,1,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The common loci represent a distinct set of the human genome sites that harbor genetic variants found in at least 1% of the population. Small somatic mutations occur at the common loci and non-common loci, i.e. csmVariants and ncsmVariants, are presumed with similar probabilities. However, our work revealed that within the coding region, common loci constituted only 1.03% of all loci, yet they accounted for 5.14% of TCGA somatic mutations. Furthermore, the small somatic mutation incidence rate at these common loci was 2.7 times that observed in the non-common. Notably, the csmVariants exhibited an impressive recurrent rate of 36.14%, which was 2.59 times of the ncsmVariants. The C-to-T transition at the CpG sites accounted for 32.41% of the csmVariants, which was 2.93 times for the ncsmVariants. Interestingly, the aging-related mutational signature contributed to 13.87% of the csmVariants, 5.5 times that of ncsmVariants. Moreover, 35.93% of the csmVariants contexts exhibited palindromic features, outperforming ncsmVariant contexts by 1.84 times. Notably, cancer patients with higher csmVariants rates had better progression-free survival. Furthermore, cancer patients with high-frequency csmVariants enriched with mismatch repair deficiency were also associated with better progression-free survival. The accumulation of csmVariants during cancerogenesis is a complex process influenced by various factors. These include the presence of a substantial percentage of palindromic sequences at csmVariants sites, the impact of aging and DNA mismatch repair deficiency. Together, these factors contribute to the higher somatic mutation incidence rates of common loci and the overall accumulation of csmVariants in cancer development.<\/jats:p>","DOI":"10.1093\/bib\/bbae065","type":"journal-article","created":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T08:35:11Z","timestamp":1709282111000},"source":"Crossref","is-referenced-by-count":1,"title":["Elevated incidence of somatic mutations at prevalent genetic sites"],"prefix":"10.1093","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2681-3873","authenticated-orcid":false,"given":"Mengyao","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Computer Science, City University of Hong Kong , 83 Tat Chee Ave, Kowloon Tong, Hong Kong , China"},{"name":"Laboratory of Gastrointestinal Cancer (Fujian Medical University) , Ministry of Education, Fuzhou , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6246-6349","authenticated-orcid":false,"given":"Shuai Cheng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Computer Science, City University of Hong Kong , 83 Tat Chee Ave, Kowloon Tong, Hong Kong , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2899-1531","authenticated-orcid":false,"given":"Bairong","family":"Shen","sequence":"additional","affiliation":[{"name":"Institutes for Systems Genetics , Frontiers Science Center for Disease-Related Molecular Network, , Chengdu, Sichuan , China"},{"name":"West China Hospital, Sichuan University , Frontiers Science Center for Disease-Related Molecular Network, , Chengdu, Sichuan , China"},{"name":"Joint Laboratory of Artificial Intelligence for Critical Care Medicine , Department of Critical Care Medicine and Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, 610212, Chengdu , China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,2,28]]},"reference":[{"issue":"7319","key":"2024030108345046800_ref1","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1038\/nature09534","article-title":"A map of human genome variation from population-scale sequencing","volume":"467","author":"Abecasis","year":"2010","journal-title":"Nature"},{"issue":"1","key":"2024030108345046800_ref2","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1093\/nar\/29.1.308","article-title":"dbSNP: the NCBI database of genetic variation","volume":"29","author":"Sherry","year":"2001","journal-title":"Nucleic Acids Res"},{"issue":"2","key":"2024030108345046800_ref3","doi-asserted-by":"crossref","first-page":"e1003301","DOI":"10.1371\/journal.pgen.1003301","article-title":"Deleterious alleles in the human genome are on average younger than neutral alleles of the same frequency","volume":"9","author":"Kiezun","year":"2013","journal-title":"PLoS Genet"},{"key":"2024030108345046800_ref4","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S0378-1119(03)00670-X","article-title":"Investigating single nucleotide polymorphism (SNP) density in the human genome and its implications for molecular evolution","volume":"312","author":"Zhao","year":"2003","journal-title":"Gene"},{"issue":"3","key":"2024030108345046800_ref5","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1038\/ng.78","article-title":"Natural selection has driven population differentiation in modern humans","volume":"40","author":"Barreiro","year":"2008","journal-title":"Nat Genet"},{"issue":"12","key":"2024030108345046800_ref6","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1002\/pro.2552","article-title":"Single nucleotide variations: biological impact and theoretical interpretation","volume":"23","author":"Katsonis","year":"2014","journal-title":"Protein Sci"},{"issue":"1","key":"2024030108345046800_ref7","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/ng947","article-title":"Human genome sequence variation and the influence of gene history, mutation and recombination","volume":"32","author":"Reich","year":"2002","journal-title":"Nat Genet"},{"issue":"3","key":"2024030108345046800_ref8","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1093\/molbev\/msi043","article-title":"CpG mutation rates in the human genome are highly dependent on local GC content","volume":"22","author":"Fryxell","year":"2005","journal-title":"Mol Biol Evol"},{"issue":"5782","key":"2024030108345046800_ref9","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1038\/287560a0","article-title":"Mutagenic deamination of cytosine residues in DNA","volume":"287","author":"Duncan","year":"1980","journal-title":"Nature"},{"issue":"4","key":"2024030108345046800_ref10","first-page":"322","article-title":"Neighboring base effects on substitution rates in pseudogenes","volume":"3","author":"Bulmer","year":"1986","journal-title":"Mol Biol Evol"},{"issue":"12","key":"2024030108345046800_ref11","doi-asserted-by":"crossref","first-page":"4692","DOI":"10.1073\/pnas.87.12.4692","article-title":"The expected equilibrium of the CpG dinucleotide in vertebrate genomes under a mutation model","volume":"87","author":"Sved","year":"1990","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"6","key":"2024030108345046800_ref12","article-title":"Palindromes in DNA-A risk for genome stability and implications in cancer","volume":"22","author":"M","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"6231","key":"2024030108345046800_ref13","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1038\/340318a0","article-title":"Palindromic sequences in heteroduplex DNA inhibit mismatch repair in yeast","volume":"340","author":"Nag","year":"1989","journal-title":"Nature"},{"issue":"11","key":"2024030108345046800_ref14","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1038\/s41588-020-00727-5","article-title":"The critical roles of somatic mutations and environmental tumor-promoting agents in cancer risk","volume":"52","author":"Balmain","year":"2020","journal-title":"Nat Genet"},{"key":"2024030108345046800_ref15","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.21778","article-title":"Non-coding cancer driver candidates identified with a sample- and position-specific model of the somatic mutation rate","volume":"6","author":"Juul","year":"2017","journal-title":"Elife"},{"issue":"9","key":"2024030108345046800_ref16","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/nbt.2681","article-title":"Systematic investigation of cancer-associated somatic point mutations in SNP databases","volume":"31","author":"Jung","year":"2013","journal-title":"Nat Biotechnol"},{"issue":"5","key":"2024030108345046800_ref17","doi-asserted-by":"crossref","first-page":"e1009557","DOI":"10.1371\/journal.pgen.1009557","article-title":"Copy number signature analysis tool and its application in prostate cancer reveals distinct mutational processes and clinical outcomes","volume":"17","author":"Wang","year":"2021","journal-title":"PLoS Genet"},{"issue":"2","key":"2024030108345046800_ref18","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.cell.2018.02.052","article-title":"An integrated TCGA pan-cancer clinical data resource to drive high-quality survival outcome analytics","volume":"173","author":"Liu","year":"2018","journal-title":"Cell"},{"issue":"5","key":"2024030108345046800_ref19","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1016\/j.cell.2017.09.042","article-title":"Universal patterns of selection in cancer and somatic tissues","volume":"171","author":"Martincorena","year":"2017","journal-title":"Cell"},{"issue":"18","key":"2024030108345046800_ref20","doi-asserted-by":"crossref","first-page":"2834","DOI":"10.1093\/bioinformatics\/btab203","article-title":"STREME: accurate and versatile sequence motif discovery","volume":"37","author":"Bailey","year":"2021","journal-title":"Bioinformatics"},{"key":"2024030108345046800_ref21","doi-asserted-by":"crossref","DOI":"10.1101\/2021.08.23.457422","article-title":"SEA: simple enrichment analysis of motifs","author":"Bailey","year":"2021"},{"issue":"1","key":"2024030108345046800_ref22","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s12859-021-03983-2","article-title":"IUPACpal: efficient identification of inverted repeats in IUPAC-encoded DNA sequences","volume":"22","author":"Alamro","year":"2021","journal-title":"BMC Bioinformatics"},{"issue":"1","key":"2024030108345046800_ref23","doi-asserted-by":"crossref","first-page":"3304","DOI":"10.1038\/s41467-020-17162-z","article-title":"Germline de novo mutation rates on exons versus introns in humans","volume":"11","author":"Rodriguez-Galindo","year":"2020","journal-title":"Nat Commun"},{"issue":"5","key":"2024030108345046800_ref24","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1101\/gr.226845.117","article-title":"Mutational signatures of DNA mismatch repair deficiency in C. Elegans and human cancers","volume":"28","author":"Meier","year":"2018","journal-title":"Genome Res"},{"issue":"W1","key":"2024030108345046800_ref25","doi-asserted-by":"crossref","first-page":"W216","DOI":"10.1093\/nar\/gkac194","article-title":"DAVID: a web server for functional enrichment analysis and functional annotation of gene lists (2021 update)","volume":"50","author":"Sherman","year":"2022","journal-title":"Nucleic Acids Res"},{"key":"2024030108345046800_ref26","doi-asserted-by":"crossref","first-page":"15042","DOI":"10.1038\/celldisc.2015.42","article-title":"SMG7 is a critical regulator of p53 stability and function in DNA damage stress response","volume":"2","author":"Luo","year":"2016","journal-title":"Cell Discov"}],"container-title":["Briefings in Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bib\/article-pdf\/25\/2\/bbae065\/56793215\/bbae065.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bib\/article-pdf\/25\/2\/bbae065\/56793215\/bbae065.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T08:35:25Z","timestamp":1709282125000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bib\/article\/doi\/10.1093\/bib\/bbae065\/7615966"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,22]]},"references-count":26,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,1,22]]}},"URL":"https:\/\/doi.org\/10.1093\/bib\/bbae065","relation":{},"ISSN":["1467-5463","1477-4054"],"issn-type":[{"type":"print","value":"1467-5463"},{"type":"electronic","value":"1477-4054"}],"subject":[],"published-other":{"date-parts":[[2024,3,1]]},"published":{"date-parts":[[2024,1,22]]},"article-number":"bbae065"}}