{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T20:12:55Z","timestamp":1780431175950,"version":"3.54.1"},"reference-count":49,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"5","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>\n                      High-grade serous ovarian cancer (HGSOC) is the most aggressive type of ovarian cancer, with a high mortality rate. Testing for alterations in\n                      <jats:italic toggle=\"yes\">BRCA1\/2<\/jats:italic>\n                      genes from tumor tissue is currently recommended as a companion diagnostic procedure for selection of patients eligible for therapy with poly (ADP-ribose) polymerase inhibitors. However, tumor testing alone does not allow for identification of patients who may have a hereditary form of the disease, whereas unselected reflex testing for germline variants is not feasible in resource-limited settings.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>MATERIALS AND METHODS<\/jats:title>\n                    <jats:p>\n                      We report real-world data from the consecutive unselected HGSOC patient population (n = 893) referred for\n                      <jats:italic toggle=\"yes\">BRCA1\/2<\/jats:italic>\n                      mutation testing between 2016 and 2023. First, we evaluated the prevalence and distribution of germline and somatic\n                      <jats:italic toggle=\"yes\">BRCA1\/2<\/jats:italic>\n                      mutations in the Serbian population. Second, we performed independent validation of the probabilistic model, LOH-Germline Inference Calculator (LOHGIC), for inference of germline origin of these alterations based on tumor purity, depth of sequencing, and allele frequency.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      The Serbian cohort shows approximately 21% overall prevalence of\n                      <jats:italic toggle=\"yes\">BRCA1\/2<\/jats:italic>\n                      pathogenic mutations in HGSOC, of which 30%-50% are germline, none detected in women over 60 years. Concordance of the LOHGIC model for prediction of germline variants with test results from a subset of 121 patients with matched tumor and blood demonstrated a sensitivity of 0.44 (95% CI, 0.14 to 0.79) and a specificity of 0.67 (95% CI, 0.41 to 0.87).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>The moderate prevalence of germline variants in the Serbian population indicates the need for selection of patients for confirmatory testing from blood. However, probabilistic models alone are not sufficiently accurate and should be complemented with information on patient history and age of onset to rule out patients with likely somatic variant origin for a cost-effective testing program.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/po-25-00819","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T19:59:13Z","timestamp":1779998353000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Validation of LOH-Germline Inference Calculator of Variant Origin on Real-World Data of Prevalence of Germline and Somatic\n                    <i>BRCA1\/2<\/i>\n                    Mutations in High-Grade Serous Ovarian Cancer in Serbia"],"prefix":"10.1200","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1986-1623","authenticated-orcid":true,"given":"Katarina","family":"\u017divi\u0107","sequence":"first","affiliation":[{"name":"Experimental Oncology Department, Institute for Oncology and Radiology of Serbia, Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Boljevi\u0107","sequence":"additional","affiliation":[{"name":"Experimental Oncology Department, Institute for Oncology and Radiology of Serbia, Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1847-0157","authenticated-orcid":true,"given":"Milana","family":"Matovi\u0107","sequence":"additional","affiliation":[{"name":"Department for Breast Tumors and Gynecologic Malignances, Clinic for Medical Oncology, Institute for Oncology and Radiology of Serbia, Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0153-3901","authenticated-orcid":true,"given":"Milica","family":"Nedeljkovi\u0107","sequence":"additional","affiliation":[{"name":"Experimental Oncology Department, Institute for Oncology and Radiology of Serbia, Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Krivoku\u0107a","sequence":"additional","affiliation":[{"name":"Department of Hereditary Cancer Genetic Counseling, Institute for Oncology and Radiology of Serbia, Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2990-0523","authenticated-orcid":true,"given":"Radmila","family":"Jankovi\u0107","sequence":"additional","affiliation":[{"name":"Experimental Oncology Department, Institute for Oncology and Radiology of Serbia, Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3102-776X","authenticated-orcid":true,"given":"Miljana","family":"Tani\u0107","sequence":"additional","affiliation":[{"name":"Experimental Oncology Department, Institute for Oncology and Radiology of Serbia, Belgrade, Serbia"},{"name":"Medical Genomics, Cancer Biology Department, UCL Cancer Institute, University College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"e_1_3_7_2_2","volume-title":"Global Cancer Observatory: Cancer Today (Version 1.1)","author":"Ferlay JEM","year":"2024","unstructured":"Ferlay JEM, Lam F, Laversanne M, et al. Global Cancer Observatory: Cancer Today (Version 1.1). Lyon, France: International Agency for Research on Cancer; 2024."},{"key":"e_1_3_7_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.21310"},{"key":"e_1_3_7_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)62146-7"},{"key":"e_1_3_7_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2013.08.017"},{"key":"e_1_3_7_6_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21456"},{"key":"e_1_3_7_7_2","doi-asserted-by":"publisher","DOI":"10.1159\/000479006"},{"key":"e_1_3_7_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2946"},{"key":"e_1_3_7_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-023-00819-1"},{"key":"e_1_3_7_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19940715)74:2<545::AID-CNCR2820740204>3.0.CO;2-Q"},{"key":"e_1_3_7_11_2","doi-asserted-by":"publisher","DOI":"10.3892\/or.2013.2541"},{"key":"e_1_3_7_12_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004347-199207000-00003"},{"key":"e_1_3_7_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2010.03.001"},{"key":"e_1_3_7_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdw142"},{"key":"e_1_3_7_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4156"},{"key":"e_1_3_7_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10166"},{"key":"e_1_3_7_17_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-4806"},{"key":"e_1_3_7_18_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.39.8545"},{"key":"e_1_3_7_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2023.11.015"},{"key":"e_1_3_7_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2644"},{"key":"e_1_3_7_21_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.02960"},{"key":"e_1_3_7_22_2","doi-asserted-by":"publisher","DOI":"10.1086\/301749"},{"key":"e_1_3_7_23_2","first-page":"265","article-title":"Breast and ovarian cancer incidence in BRCA1-mutation carriers. Breast Cancer Linkage Consortium","volume":"56","author":"Easton DF","year":"1995","unstructured":"Easton DF, Ford D, Bishop DT: Breast and ovarian cancer incidence in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Am J Hum Genet 56:265-271, 1995","journal-title":"Am J Hum Genet"},{"key":"e_1_3_7_24_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.09.1066"},{"key":"e_1_3_7_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40290-021-00399-4"},{"key":"e_1_3_7_26_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.183053.114"},{"key":"e_1_3_7_27_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1005965"},{"key":"e_1_3_7_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2018.09.008"},{"key":"e_1_3_7_29_2","article-title":"Inference of germline mutational status and evaluation of loss of heterozygosity in high-depth, tumor-only sequencing data","author":"Khiabanian H","unstructured":"Khiabanian H, Hirshfield KM, Goldfinger M, et al: Inference of germline mutational status and evaluation of loss of heterozygosity in high-depth, tumor-only sequencing data. JCO Precis Oncol 10.1200\/PO.17.00148","journal-title":"JCO Precis Oncol"},{"key":"e_1_3_7_30_2","article-title":"Germline testing data validate inferences of mutational status for variants detected from tumor-only sequencing","author":"Jalloul N","unstructured":"Jalloul N, Gomy I, Stokes S, et al: Germline testing data validate inferences of mutational status for variants detected from tumor-only sequencing. JCO Precis Oncol 10.1200\/PO.21.00279","journal-title":"JCO Precis Oncol"},{"key":"e_1_3_7_31_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.d2304"},{"key":"e_1_3_7_32_2","doi-asserted-by":"crossref","unstructured":"Cerami E Gao J Dogrusoz U et al: The cBio cancer genomics portal: An open platform for exploring multidimensional cancer genomics data. Cancer Discov 2:401-404 2012","DOI":"10.1158\/2159-8290.CD-12-0095"},{"key":"e_1_3_7_33_2","unstructured":"Reference deleted"},{"key":"e_1_3_7_34_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1810858"},{"key":"e_1_3_7_35_2","doi-asserted-by":"publisher","DOI":"10.1111\/1471-0528.16975"},{"key":"e_1_3_7_36_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16091682"},{"key":"e_1_3_7_37_2","doi-asserted-by":"publisher","DOI":"10.5468\/ogs.20033"},{"key":"e_1_3_7_38_2","doi-asserted-by":"publisher","DOI":"10.21037\/atm-20-6827"},{"key":"e_1_3_7_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/s10038-019-0562-z"},{"key":"e_1_3_7_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2004.10.011"},{"key":"e_1_3_7_41_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.21536"},{"key":"e_1_3_7_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2011.01.020"},{"key":"e_1_3_7_43_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-019-5535-2"},{"key":"e_1_3_7_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2023.154475"},{"key":"e_1_3_7_45_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13053-021-00169-y"},{"key":"e_1_3_7_46_2","doi-asserted-by":"publisher","DOI":"10.1111\/jog.14090"},{"key":"e_1_3_7_47_2","doi-asserted-by":"publisher","DOI":"10.1111\/cas.15166"},{"key":"e_1_3_7_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature25778"},{"key":"e_1_3_7_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jncc.2022.12.001"},{"key":"e_1_3_7_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2023.08.011"}],"container-title":["JCO Precision Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/PO-25-00819","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T19:59:26Z","timestamp":1780430366000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/PO-25-00819"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":49,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1200\/PO-25-00819"],"URL":"https:\/\/doi.org\/10.1200\/po-25-00819","relation":{},"ISSN":["2473-4284"],"issn-type":[{"value":"2473-4284","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5]]},"assertion":[{"value":"2025-08-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-12","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2500819"}}