{"doi":"10.36401/jipo-23-2","title":"Limited Independent Follow-Up with Germline Testing of Variants Detected in\n                    <i>BRCA1</i>\n                    and\n                    <i>BRCA2</i>\n                    by Tumor-Only Sequencing","abstract":"<jats:title>ABSTRACT</jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction</jats:title>\n                    <jats:p>Genomic profiling is performed in patients with advanced or metastatic cancer, in order to direct cancer treatment, often sequencing tumor-only, without a matched germline comparator. However, because many of the genes analyzed on tumor profiling overlap with those known to be associated with hereditary cancer predisposition syndromes (HCPS), tumor-only profiling can unknowingly uncover germline pathogenic (P) and likely pathogenic variants (LPV). In this study, we evaluated the number of patients with P/LPVs identified in BRCA1 and BRCA2 (BRCA1/2) via tumor-only profiling, then determined the germline testing outcomes for those patients.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods</jats:title>\n                    <jats:p>A retrospective chart review was performed to identify patients with BRCA1/2 variants on tumor-only genomic profiling, and whether they had germline testing.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Results</jats:title>\n                    <jats:p>This study found that of 2923 patients with 36 tumor types who underwent tumor-only testing, 554 had a variant in BRCA1/2 (19.0%); 119 of the 554 patients (21.5%) had a P/LP BRCA1/2 variant, representing 4.1% of the overall population who underwent genomic profiling. Seventy-three (61.3%) of 119 patients with BRCA1/2 P/LPV on tumor-only testing did not undergo germline testing, 34 (28.6%) had already had germline testing before tumor-only testing, and 12 (10.1%) underwent germline testing after tumor-only testing. Twenty-eight germline BRCA1/2 P/LPVs were detected, 24 in those who had prior germline testing, and 4 among the 12 patients who had germline testing after tumor-only testing.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion</jats:title>\n                    <jats:p>Tumor-only testing is likely to identify P/LPVs in BRCA1/2. Efforts to improve follow-up germline testing is needed to improve identification of germline BRCA1/2 alterations.</jats:p>\n                  </jats:sec>","journal":"Journal of Immunotherapy and Precision Oncology","year":2024,"id":612811,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"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":1578071,"name":"Molly Daniels","orcid":null,"position":1,"is_corresponding":false},{"id":348521,"name":"Burak Uzunparmak","orcid":"0000-0002-9791-8904","position":2,"is_corresponding":false},{"id":1578072,"name":"Ecaterina E. Ileana Dumbrava","orcid":null,"position":3,"is_corresponding":false},{"id":546980,"name":"Ying Yuan","orcid":"0000-0002-3922-9553","position":4,"is_corresponding":false},{"id":33069,"name":"Keyur P. Patel","orcid":"0000-0001-5081-2427","position":5,"is_corresponding":false},{"id":1578073,"name":"Nadine Rayes","orcid":null,"position":6,"is_corresponding":false},{"id":1578074,"name":"Jacqueline Harkenrider","orcid":null,"position":7,"is_corresponding":false},{"id":352364,"name":"Chetna Wathoo","orcid":null,"position":8,"is_corresponding":false},{"id":1578075,"name":"Jennifer Veazie","orcid":null,"position":9,"is_corresponding":false},{"id":1578076,"name":"Krystle A. Luna","orcid":null,"position":10,"is_corresponding":false},{"id":1285098,"name":"Wanlin Wang","orcid":"0000-0003-4298-7168","position":11,"is_corresponding":false},{"id":1285620,"name":"Chacha Horombe","orcid":null,"position":12,"is_corresponding":false},{"id":226645,"name":"Milind Javle","orcid":"0000-0001-9158-0941","position":13,"is_corresponding":false},{"id":269051,"name":"Jordi Rodon Ahnert","orcid":null,"position":14,"is_corresponding":false},{"id":89413,"name":"Timothy A. Yap","orcid":"0000-0002-2154-3309","position":15,"is_corresponding":false},{"id":225491,"name":"Banu Arun","orcid":"0000-0002-5475-8509","position":16,"is_corresponding":false},{"id":40782,"name":"Karen H. Lu","orcid":"0000-0002-5317-9927","position":17,"is_corresponding":false},{"id":69934,"name":"Funda Meric-Bernstam","orcid":null,"position":18,"is_corresponding":false},{"id":1578069,"name":"Carol J. Nowlen","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Limited Independent Follow-Up with Germline Testing of Variants Detected in\n                    <i>BRCA1</i>\n                    and\n                    <i>BRCA2</i>\n                    by Tumor-Only Sequencing","abstract":"<jats:title>ABSTRACT</jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction</jats:title>\n                    <jats:p>Genomic profiling is performed in patients with advanced or metastatic cancer, in order to direct cancer treatment, often sequencing tumor-only, without a matched germline comparator. However, because many of the genes analyzed on tumor profiling overlap with those known to be associated with hereditary cancer predisposition syndromes (HCPS), tumor-only profiling can unknowingly uncover germline pathogenic (P) and likely pathogenic variants (LPV). In this study, we evaluated the number of patients with P/LPVs identified in BRCA1 and BRCA2 (BRCA1/2) via tumor-only profiling, then determined the germline testing outcomes for those patients.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods</jats:title>\n                    <jats:p>A retrospective chart review was performed to identify patients with BRCA1/2 variants on tumor-only genomic profiling, and whether they had germline testing.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Results</jats:title>\n                    <jats:p>This study found that of 2923 patients with 36 tumor types who underwent tumor-only testing, 554 had a variant in BRCA1/2 (19.0%); 119 of the 554 patients (21.5%) had a P/LP BRCA1/2 variant, representing 4.1% of the overall population who underwent genomic profiling. Seventy-three (61.3%) of 119 patients with BRCA1/2 P/LPV on tumor-only testing did not undergo germline testing, 34 (28.6%) had already had germline testing before tumor-only testing, and 12 (10.1%) underwent germline testing after tumor-only testing. Twenty-eight germline BRCA1/2 P/LPVs were detected, 24 in those who had prior germline testing, and 4 among the 12 patients who had germline testing after tumor-only testing.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion</jats:title>\n                    <jats:p>Tumor-only testing is likely to identify P/LPVs in BRCA1/2. Efforts to improve follow-up germline testing is needed to improve identification of germline BRCA1/2 alterations.</jats:p>\n                  </jats:sec>","is_dataset_classified":null,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"38327755","pmcid":"PMC10846638","openalex_id":"https://openalex.org/W4390031671","authors":[],"funders":[{"funder_name":"National Institutes of Health","grant_id":"3P30CA016672-41S4","title":"Cancer Center Support (CORE) Grant"},{"funder_name":"National Institutes of Health","grant_id":"3UL1TR003167-02S4","title":"Center for Clinical and Translational Sciences (CCTS)"},{"funder_name":"National Institutes of Health","grant_id":"4UL1TR000371-10","title":"Center for Clinical and Translational Sciences (CCTS)"}],"total_grants":3,"fwci":0.2164,"citation_percentile":0.64718468,"influential_citations":0,"citation_trend":[{"year":2024,"count":1}],"oa_status":"gold","license":"cc-by-nc-nd","oa_locations":[{"url":"https://meridian.allenpress.com/innovationsjournals-JIPO/article-pdf/7/1/7/3324497/i2590-017x-7-1-7.pdf","host_type":"journal"},{"url":"https://meridian.allenpress.com/innovationsjournals-JIPO/article-pdf/7/1/7/3324497/i2590-017x-7-1-7.pdf","host_type":"publisher"},{"url":"https://doi.org/10.36401/jipo-23-2","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/38327755","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/10846638","host_type":"repository"},{"url":"https://digitalcommons.library.tmc.edu/uthmed_docs/1733","host_type":"repository"},{"url":"https://doaj.org/article/1c82c80e6fbe4a119579d33a7fda0372","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10846638/pdf/i2590-017X-7-1-7.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC10846638","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC10846638?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.36401/JIPO-23-2","host_type":""},{"url":"https://doi.org/https://doi.org/10.36401/JIPO-23-2","host_type":""}],"fields_of_study":["BRCA gene mutations in cancer","Genomics and Rare Diseases","Cancer Genomics and Diagnostics","03 medical and health sciences","0302 clinical medicine"],"mesh_terms":[],"keywords":["Germline","Genetic testing","Medicine","Germline mutation","Oncology","Cancer","Internal medicine","Genetics","Biology","Gene","Mutation","BRCA1","BRCA2","Germline Testing","Tumor-only Testing","Obstetrics and Gynecology","610","Neoplasms. Tumors. Oncology. Including cancer and carcinogens","RC581-607","Maternal and Child Health","Medical Specialties","Medicine and Health Sciences","Women's Health","Public Health","Immunologic diseases. Allergy","RC254-282","Research Article"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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