{"doi":"10.1093/nar/gkaa019","title":"Prevalence and architecture of posttranscriptionally impaired synonymous mutations in 8,320 genomes across 22 cancer types","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>Somatic synonymous mutations are one of the most frequent genetic variants occurring in the coding region of cancer genomes, while their contributions to cancer development remain largely unknown. To assess whether synonymous mutations involved in post-transcriptional regulation contribute to the genetic etiology of cancers, we collected whole exome data from 8,320 patients across 22 cancer types. By employing our developed algorithm, PIVar, we identified a total of 22,948 posttranscriptionally impaired synonymous SNVs (pisSNVs) spanning 2,042 genes. In addition, 35 RNA binding proteins impacted by these identified pisSNVs were significantly enriched. Remarkably, we discovered markedly elevated ratio of somatic pisSNVs across all 22 cancer types, and a high pisSNV ratio was associated with worse patient survival in five cancer types. Intriguing, several well-established cancer genes, including PTEN, RB1 and PIK3CA, appeared to contribute to tumorigenesis at both protein function and posttranscriptional regulation levels, whereas some pisSNV-hosted genes, including UBR4, EP400 and INTS1, exerted their function during carcinogenesis mainly via posttranscriptional mechanisms. Moreover, we predicted three drugs associated with two pisSNVs, and numerous compounds associated with expression signature of pisSNV-hosted genes. Our study reveals the prevalence and clinical relevance of pisSNVs in cancers, and emphasizes the importance of considering posttranscriptional impaired synonymous mutations in cancer biology.</jats:p>","journal":"Nucleic Acids Research","year":2020,"id":604018,"datarank":0.6090664515819629,"base_score":4.060443010546419,"endowment":4.060443010546419,"self_citation_contribution":0.6090664515819629,"citation_network_contribution":0.0,"self_endowment_contribution":0.6090664515819629,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":57,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1549606,"name":"Wenqing Wei","orcid":null,"position":1,"is_corresponding":false},{"id":852825,"name":"Qinglan Li","orcid":"0000-0003-0160-8774","position":2,"is_corresponding":false},{"id":1549607,"name":"Meiying Xue","orcid":null,"position":3,"is_corresponding":false},{"id":1549608,"name":"Xiaohui Shi","orcid":null,"position":4,"is_corresponding":false},{"id":127074,"name":"Xianfeng Li","orcid":null,"position":5,"is_corresponding":false},{"id":317589,"name":"Fengbiao Mao","orcid":"0000-0003-0852-4266","position":6,"is_corresponding":false},{"id":1549609,"name":"Zhongsheng Sun","orcid":"0000-0003-1864-4819","position":7,"is_corresponding":false},{"id":564586,"name":"Huajing Teng","orcid":"0000-0001-9952-3618","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Prevalence and architecture of posttranscriptionally impaired synonymous mutations in 8,320 genomes across 22 cancer types","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>Somatic synonymous mutations are one of the most frequent genetic variants occurring in the coding region of cancer genomes, while their contributions to cancer development remain largely unknown. To assess whether synonymous mutations involved in post-transcriptional regulation contribute to the genetic etiology of cancers, we collected whole exome data from 8,320 patients across 22 cancer types. By employing our developed algorithm, PIVar, we identified a total of 22,948 posttranscriptionally impaired synonymous SNVs (pisSNVs) spanning 2,042 genes. In addition, 35 RNA binding proteins impacted by these identified pisSNVs were significantly enriched. Remarkably, we discovered markedly elevated ratio of somatic pisSNVs across all 22 cancer types, and a high pisSNV ratio was associated with worse patient survival in five cancer types. Intriguing, several well-established cancer genes, including PTEN, RB1 and PIK3CA, appeared to contribute to tumorigenesis at both protein function and posttranscriptional regulation levels, whereas some pisSNV-hosted genes, including UBR4, EP400 and INTS1, exerted their function during carcinogenesis mainly via posttranscriptional mechanisms. Moreover, we predicted three drugs associated with two pisSNVs, and numerous compounds associated with expression signature of pisSNV-hosted genes. Our study reveals the prevalence and clinical relevance of pisSNVs in cancers, and emphasizes the importance of considering posttranscriptional impaired synonymous mutations in cancer biology.</jats:p>","is_dataset_classified":null,"base_score":4.060443010546419,"endowment":4.060443010546419,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"31950163","pmcid":"PMC7026592","openalex_id":"https://openalex.org/W3000249748","authors":[],"funders":[{"funder_name":"National Natural Science Foundation of China","grant_id":"31872237","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"31911530148","title":null},{"funder_name":"National Key Research and Development Program of China","grant_id":"2016YFC0900400","title":null}],"total_grants":3,"fwci":2.3864,"citation_percentile":0.89659695,"influential_citations":0,"citation_trend":[{"year":2020,"count":5},{"year":2021,"count":8},{"year":2022,"count":11},{"year":2023,"count":8},{"year":2024,"count":18},{"year":2025,"count":7}],"oa_status":"gold","license":"cc-by-nc","oa_locations":[{"url":"https://academic.oup.com/nar/article-pdf/48/3/1192/32533191/gkaa019.pdf","host_type":"journal"},{"url":"https://academic.oup.com/nar/article-pdf/48/3/1192/32533191/gkaa019.pdf","host_type":"publisher"},{"url":"http://academic.oup.com/nar/article-pdf/48/3/1192/32533191/gkaa019.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1093/nar/gkaa019","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/31950163","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/7026592","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC7026592","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC7026592?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["RNA Research and Splicing","RNA and protein synthesis mechanisms","Genomics and Chromatin Dynamics","Adult","Aged","Calmodulin-Binding Proteins","Carcinogenesis","Class I Phosphatidylinositol 3-Kinases","DNA Helicases","DNA-Binding Proteins","Exome","Female","Gene Expression Regulation, Neoplastic","Genome, Human","Humans","Kaplan-Meier Estimate","Male","Middle Aged","Neoplasms","PTEN Phosphohydrolase","Progression-Free Survival","Protein Processing, Post-Translational","Quantitative Trait Loci","Retinoblastoma Binding Proteins","Silent Mutation","Ubiquitin-Protein Ligases","Wnt1 Protein"],"mesh_terms":["Silent Mutation","Progression-Free Survival","Adult","Aged","Calmodulin-Binding Proteins","DNA Helicases","DNA-Binding Proteins","Female","Humans","Male","Middle Aged","Neoplasms","Protein Processing, Post-Translational","Genome, Human","Gene Expression Regulation, Neoplastic","Quantitative Trait Loci","Ubiquitin-Protein Ligases","PTEN Phosphohydrolase","Wnt1 Protein","Kaplan-Meier Estimate","Retinoblastoma Binding Proteins","Class I Phosphatidylinositol 3-Kinases","Exome","Carcinogenesis"],"keywords":["Biology","Carcinogenesis","Genetics","Gene","PTEN","Cancer","Genome","Exome","Mutation","Exome sequencing"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"pdb"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-29T23:12:11.599312Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}