| Title |
BRCA1 and BRCA2 genetic testing—pitfalls and recommendations for managing variants of uncertain clinical significance
|
|---|---|
| Published in |
Annals of Oncology, July 2015
|
| DOI | 10.1093/annonc/mdv278 |
| Pubmed ID | |
| Authors |
D.M. Eccles, G. Mitchell, A.N.A. Monteiro, R. Schmutzler, F.J. Couch, A.B. Spurdle, E.B. Gómez-García, on behalf of the ENIGMA Clinical Working Group, R. Driessen, N.M. Lindor, M.J. Blok, P. Moller, M. de la Hoya, T. Pal, S. Domchek, K. Nathanson, C. Van Asperen, O. Diez, K. Rheim, D. Stoppa-Lyonnet, M. Parsons, D. Goldgar |
| Abstract |
Increasing use of BRCA1/2 testing for tailoring cancer treatment and extension of testing to tumour tissue for somatic mutation is moving BRCA1/2 mutation screening from a primarily prevention arena delivered by specialist genetic services into mainstream oncology practice. A considerable number of gene tests will identify rare variants where clinical significance cannot be inferred from sequence information alone. The proportion of Variants of Uncertain clinical Significance (VUS) is likely to grow with lower thresholds for testing and laboratory providers with less experience of BRCA. Most VUS will not be associated with a high risk of cancer but a misinterpreted VUS has the potential to lead to mismanagement of both the patient and their relatives. Members of the Clinical Working Group of ENIGMA (Evidence-based Network for the Interpretation of Germline Mutant Alleles) global consortium (www.enigmaconsortium.org) observed wide variation in practices in reporting, disclosure and clinical management of patients with a VUS. Examples from current clinical practice are presented and discussed to illustrate potential pitfalls, explore factors contributing to misinterpretation, and propose approaches to improving clarity. Clinicians, patients and their relatives would all benefit from an improved level of genetic literacy. Genetic laboratories working with clinical geneticists need to agree on a clinically clear and uniform format for reporting BRCA test results to non-geneticists. An international consortium of experts, collecting and integrating all available lines of evidence and classifying variants according to an internationally recognized system will facilitate reclassification of variants for clinical use. |
X Demographics
The data shown below were collected from the profiles of 19 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 9 | 47% |
| Italy | 1 | 5% |
| Unknown | 9 | 47% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 15 | 79% |
| Practitioners (doctors, other healthcare professionals) | 2 | 11% |
| Science communicators (journalists, bloggers, editors) | 1 | 5% |
| Scientists | 1 | 5% |
Mendeley readers
The data shown below were compiled from readership statistics for 268 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | <1% |
| Kenya | 1 | <1% |
| Ireland | 1 | <1% |
| Canada | 1 | <1% |
| Unknown | 264 | 99% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 41 | 15% |
| Student > Ph. D. Student | 35 | 13% |
| Researcher | 34 | 13% |
| Student > Bachelor | 23 | 9% |
| Other | 22 | 8% |
| Other | 50 | 19% |
| Unknown | 63 | 24% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 81 | 30% |
| Biochemistry, Genetics and Molecular Biology | 56 | 21% |
| Agricultural and Biological Sciences | 32 | 12% |
| Nursing and Health Professions | 5 | 2% |
| Psychology | 4 | 1% |
| Other | 18 | 7% |
| Unknown | 72 | 27% |
Attention Score in Context
This research output has an Altmetric Attention Score of 15. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 01 January 2016.
All research outputs
#2,514,682
of 26,017,215 outputs
Outputs from Annals of Oncology
#1,339
of 7,992 outputs
Outputs of similar age
#30,679
of 279,630 outputs
Outputs of similar age from Annals of Oncology
#15
of 99 outputs
Altmetric has tracked 26,017,215 research outputs across all sources so far. Compared to these this one has done well and is in the 89th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 7,992 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 14.6. This one has done well, scoring higher than 82% of its peers.
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We're also able to compare this research output to 99 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 84% of its contemporaries.