{"doi":"10.1101/112672","title":"Discovery and reporting of clinically-relevant germline variants in advanced cancer patients assessed using whole-exome sequencing","abstract":"<jats:title>Abstract</jats:title>\n                <jats:sec>\n                  <jats:title>Purpose</jats:title>\n                  <jats:p>In precision cancer care, WES-based analysis of tumor-normal samples helps reveal somatic alterations but can also identify cancer-associated germline variants important for disease surveillance, treatment choice and cancer prevention. WES can also identify germline secondary findings impacting risk of cardiac, neurodegenerative or metabolic diseases. In patients with advanced cancer, the frequency of reportable secondary findings encountered with WES is not well defined.</jats:p>\n                </jats:sec>\n                <jats:sec>\n                  <jats:title>Methods</jats:title>\n                  <jats:p>To address this question, we analyzed a cohort of 343 patients with advanced, metastatic cancer for whom we have performed tumor and germline WES interrogating more than 21,000 genes using a CLIA/CLEP approved assay.</jats:p>\n                </jats:sec>\n                <jats:sec>\n                  <jats:title>Results</jats:title>\n                  <jats:p>17% of patients in our cohort have one or more reportable germline variants, including patients with pathogenic variants in the BRCA1 and BRCA2 genes. The frequency of non-cancer clinically relevant germline variants (8.8%) was within the range of two control non-cancer cohorts (11.0% and 6.5%). The frequency of variants in cancer-associated genes was significantly higher (p&lt;0.0005) in our advanced cancer cohort (8.2%) compared to control cohorts (2.7% and 3.8%). More than 50% of patients with reportable germline cancer variants had a family history of cancer.</jats:p>\n                </jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion</jats:title>\n                  <jats:p>these results stress the importance of returning germline results found during somatic genomic tumor testing.</jats:p>\n                </jats:sec>","journal":null,"year":null,"id":601430,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"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":52031,"name":"Alessandro Romanel","orcid":"0000-0003-4855-8620","position":1,"is_corresponding":false},{"id":1542146,"name":"Kenneth W. Eng","orcid":null,"position":2,"is_corresponding":false},{"id":381084,"name":"Hanna Rennert","orcid":"0000-0002-1759-2562","position":3,"is_corresponding":false},{"id":810005,"name":"Adrian Y. Tan","orcid":"0000-0001-6969-6606","position":4,"is_corresponding":false},{"id":1542147,"name":"Yaohua Xue","orcid":null,"position":5,"is_corresponding":false},{"id":259315,"name":"Joanna Cyrta","orcid":"0000-0002-0216-5330","position":6,"is_corresponding":false},{"id":562837,"name":"Juan Miguel Mosquera","orcid":"0000-0003-4666-6476","position":7,"is_corresponding":false},{"id":41062,"name":"Andrea Sboner","orcid":"0000-0001-6915-3070","position":8,"is_corresponding":false},{"id":1044299,"name":"Ivan Iossifov","orcid":"0000-0003-0035-8312","position":9,"is_corresponding":false},{"id":237944,"name":"Steven M. Lipkin","orcid":"0000-0002-0603-9139","position":10,"is_corresponding":false},{"id":109227,"name":"Jenny Xiang","orcid":"0000-0003-0484-2769","position":11,"is_corresponding":false},{"id":246048,"name":"Xiaojun Feng","orcid":"0000-0003-3490-2873","position":12,"is_corresponding":false},{"id":559929,"name":"Peter Nelson","orcid":null,"position":13,"is_corresponding":false},{"id":85728,"name":"Himisha Beltran","orcid":"0000-0003-3259-2226","position":14,"is_corresponding":false},{"id":255748,"name":"Colin C. Pritchard","orcid":"0000-0002-2461-1557","position":15,"is_corresponding":false},{"id":13152,"name":"Mark A. Rubin","orcid":"0000-0002-8321-9950","position":16,"is_corresponding":false},{"id":35285,"name":"Francesca Demichelis","orcid":"0000-0002-8266-8631","position":17,"is_corresponding":false},{"id":41043,"name":"Olivier Elemento","orcid":"0000-0002-8061-9617","position":18,"is_corresponding":false},{"id":109215,"name":"Tuo Zhang","orcid":"0000-0001-5396-918X","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Discovery and reporting of clinically-relevant germline variants in advanced cancer patients assessed using whole-exome sequencing","abstract":"<jats:title>Abstract</jats:title>\n                <jats:sec>\n                  <jats:title>Purpose</jats:title>\n                  <jats:p>In precision cancer care, WES-based analysis of tumor-normal samples helps reveal somatic alterations but can also identify cancer-associated germline variants important for disease surveillance, treatment choice and cancer prevention. WES can also identify germline secondary findings impacting risk of cardiac, neurodegenerative or metabolic diseases. In patients with advanced cancer, the frequency of reportable secondary findings encountered with WES is not well defined.</jats:p>\n                </jats:sec>\n                <jats:sec>\n                  <jats:title>Methods</jats:title>\n                  <jats:p>To address this question, we analyzed a cohort of 343 patients with advanced, metastatic cancer for whom we have performed tumor and germline WES interrogating more than 21,000 genes using a CLIA/CLEP approved assay.</jats:p>\n                </jats:sec>\n                <jats:sec>\n                  <jats:title>Results</jats:title>\n                  <jats:p>17% of patients in our cohort have one or more reportable germline variants, including patients with pathogenic variants in the BRCA1 and BRCA2 genes. The frequency of non-cancer clinically relevant germline variants (8.8%) was within the range of two control non-cancer cohorts (11.0% and 6.5%). The frequency of variants in cancer-associated genes was significantly higher (p&lt;0.0005) in our advanced cancer cohort (8.2%) compared to control cohorts (2.7% and 3.8%). More than 50% of patients with reportable germline cancer variants had a family history of cancer.</jats:p>\n                </jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion</jats:title>\n                  <jats:p>these results stress the importance of returning germline results found during somatic genomic tumor testing.</jats:p>\n                </jats:sec>","is_dataset_classified":null,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"23304386","pmcid":null,"openalex_id":"https://openalex.org/W2594306613","authors":[],"funders":[{"funder_name":"National Institutes of Health","grant_id":"5T32GM007739-30","title":"Weill Cornell/Rockefeller/Sloan-Kettering MST Program"},{"funder_name":"National Institutes of Health","grant_id":"5R01CA194547-03","title":"The identification and validation of mechanisms and biomarkers for relapse in diffuse large B-cell lymphoma"}],"total_grants":2,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[{"year":2019,"count":1},{"year":2020,"count":1}],"oa_status":"green","license":"cc-by-nc-nd","oa_locations":[{"url":"https://www.biorxiv.org/content/biorxiv/early/2017/03/01/112672.full.pdf","host_type":"repository"},{"url":"https://www.biorxiv.org/content/biorxiv/early/2017/03/01/112672.full.pdf","host_type":"repository"},{"url":"https://syndication.highwire.org/content/doi/10.1101/112672","host_type":"publisher"},{"url":"https://doi.org/10.1101/112672","host_type":"repository"},{"url":"https://dx.doi.org/10.1101/112672","host_type":""},{"url":"http://dx.doi.org/10.1101/112672","host_type":""}],"fields_of_study":["Cancer Genomics and Diagnostics","Genomics and Rare Diseases","Genetic factors in colorectal cancer","0301 basic medicine","0303 health sciences","03 medical and health sciences"],"mesh_terms":[],"keywords":["Germline","Cancer","Exome sequencing","Cohort","Medicine","Germline mutation","Oncology","Exome","Somatic cell","Disease","Internal medicine","Genetics","Bioinformatics","Biology","Gene","Mutation"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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