ArticleJournal of clinical oncology : official journal of the American Society of Clinical Oncology2008
Clinically applicable models to characterize BRCA1 and BRCA2 variants of uncertain significance.
Article in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 81 citations in OpenAlex.
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- Value of the loss of heterozygosity to BRCA1 variant classification.NPJ breast cancer · 2022Article
- Identification of a Cowden syndrome patient with a novel PTEN mutation and establishment of patient-derived induced pluripotent stem cells.In vitro cellular & developmental biology. Animal · 2022Article
- Functional pre-therapeutic evaluation by genome editing of variants of uncertain significance of essential tumor suppressor genes.Genome medicine · 2021Article
- Classification of 101 BRCA1 and BRCA2 variants of uncertain significance by cosegregation study: A powerful approach.American journal of human genetics · 2021Article
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- The p.Ser64Leu and p.Pro104Leu missense variants of PALB2 identified in familial pancreatic cancer patients compromise the DNA damage response.Human mutation · 2021Article
- Genetic Testing to Guide Risk-Stratified Screens for Breast Cancer.Journal of personalized medicine · 2019Review
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- Metaplastic breast cancer in a patient with neurofibromatosis type 1 and somatic loss of heterozygosity.Cold Spring Harbor molecular case studies · 2018Review
- Characterization of mutations in BRCA1/2 and the relationship with clinic-pathological features of breast cancer in a hereditarily high-risk sample of chinese population.Oncology letters · 2018Article
- Analysis of BRCA1/2 mutation spectrum and prevalence in unselected Chinese breast cancer patients by next-generation sequencing.Journal of cancer research and clinical oncology · 2017Article
- Clinically Significant Unclassified Variants inCancer research and treatment · 2017Article
- Adding In Silico Assessment of Potential Splice Aberration to the Integrated Evaluation of BRCA Gene Unclassified Variants.Human mutation · 2016Article
- Genetic counselors' practices and confidence regarding variant of uncertain significance results and reclassification from BRCA testing.Clinical genetics · 2015Article
- Epidemiology of Patients with Ovarian Cancer with and Without a BRCA1/2 Mutation.Molecular diagnosis & therapy · 2015Review
- Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
purposeTwenty percent of individuals with a strong family and/or personal history of breast and ovarian cancer carry a deleterious mutation in BRCA1 or BRCA2. Identification of mutations in these genes is extremely beneficial for patients pursuing risk reduction strategies. Approximately 7% of individuals who have genetic testing of BRCA1 and BRCA2 carry a variant of uncertain significance (VUS), making clinical management less certain. The majority of identified VUS occur only in one to two individuals; these variants are not able to be classified using current classification models with segregation analysis components.
methodsTo develop a clinically applicable method that can predict the pathogenicity of VUS that does not require familial information or segregation analysis, we identified characteristics of breast or ovarian tumors that distinguished sporadic tumors from tumors with BRCA1 or BRCA2 mutations. Study participants included individuals with known deleterious mutations in BRCA1 or BRCA2 and individuals with classified or unclassified BRCA variants.
resultsWe applied the models to 57 tumors with 43 different deleterious BRCA mutations and 57 tumors with 54 unique classified and unclassified BRCA variants. Of the 33 previously unclassified VUS studied, we found evidence of neutrality for 21.
conclusionOur models showed 98% sensitivity and 76% specificity for predicting classified DNA changes. We classified 64% of unknown variants as neutral. Classification of VUS as neutral will have immediate benefit for those individuals and their family members. These models are adaptable for the clinic and will be useful for individuals with limited available family history.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.