{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T12:03:13Z","timestamp":1791028993372,"version":"4.1.0"},"reference-count":20,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2005,4,1]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p> To obtain and compare the probabilities of finding a mutation in the BRCA1 or BRCA2 genes, the clinical features, and the family history among patients with an unclassified variant (UV) and those with a pathogenic mutation. <\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p> The study included 70 patients: 24 with a UV (BRCA1, n = 4; BRCA2, n = 19; both, n = 1), and 46 with a mutation (BRCA1, n = 32; BRCA2, n = 14). Two of the UVs were novel variants; the rest had been reported previously as UVs. Probabilities of finding a mutation were retrospectively obtained using BRCAPRO and Myriad II programs. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> The probability to detect a mutation was significantly lower in the group of patients with a UV than in those with a mutation (BRCAPRO [mean \u00b1 standard deviation], 0.297 \u00b1 0.312 v 0.627 \u00b1 0.315, P = .001; and Myriad II, 0.124 \u00b1 0.090 v 0.283 \u00b1 0.176, P = .001, respectively). Independent predictive factors of finding either a UV or a mutation were number of affected relatives (2.9 \u00b1 1.4 v 4.0 \u00b1 1.9; P = .039) and number of tumors among relatives (3.3 \u00b1 1.4 v 4.4 \u00b1 1.8; P = .031), respectively. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p> The combined data about the predictive models show significant differences between both groups. Individual probabilities can be regarded as a help to guide the clinical management of patients with a UV in those genes. However, a definitive conclusion about the pathogenicity of a UV can not be obtained from the clinical features alone, but only in combination with biochemical and epidemiologic data. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.2005.07.013","type":"journal-article","created":{"date-parts":[[2005,3,30]],"date-time":"2005-03-30T23:43:15Z","timestamp":1112226195000},"page":"2185-2190","source":"Crossref","is-referenced-by-count":18,"title":["Patients With an Unclassified Genetic Variant in the <i>BRCA1<\/i> or <i>BRCA2<\/i> Genes Show Different Clinical Features From Those With a Mutation"],"prefix":"10.1200","volume":"23","author":[{"given":"Encarna B.","family":"G\u00f3mez-Garc\u00eda","sequence":"first","affiliation":[{"name":"From the Department of Clinical Genetics, University Hospital and Research Institute Growth & Development, and Department of Methodology and Statistics, the University of Maastricht, Maastricht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ton","family":"Ambergen","sequence":"additional","affiliation":[{"name":"From the Department of Clinical Genetics, University Hospital and Research Institute Growth & Development, and Department of Methodology and Statistics, the University of Maastricht, Maastricht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marinus J.","family":"Blok","sequence":"additional","affiliation":[{"name":"From the Department of Clinical Genetics, University Hospital and Research Institute Growth & Development, and Department of Methodology and Statistics, the University of Maastricht, Maastricht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur","family":"van den Wijngaard","sequence":"additional","affiliation":[{"name":"From the Department of Clinical Genetics, University Hospital and Research Institute Growth & Development, and Department of Methodology and Statistics, the University of Maastricht, Maastricht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"R1","unstructured":"National Human Genome Research Institute: Breast Cancer Information Core (BIC) database: An open access on-line breast cancer mutation data base . http:\/\/research.nhgri.nih.gov\/bic\/"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1016\/S1570-0232(02)00696-7"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1089\/10906570260199375"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0237285100"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1086\/301871"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1089\/10906570260199357"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2003.015867"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1086\/424388"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.10337"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1086\/301670"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1998.16.7.2417"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1999.6026"},{"key":"R14","unstructured":"Hogervorst FB, Nederlof PM, Gille JJ, et al: Large genomic deletions and duplications in the BRCA1 gene identified by a novel quantitative method. 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