Variants of uncertain significance in BRCA: a harbinger of ethical and policy issues to come?

After two decades of genetic testing and research, the BRCA1 and BRCA2 genes are two of the most well-characterized genes in the human genome. As a result, variants of uncertain significance (VUS; also called variants of unknown significance) are reported less frequently than for genes that have bee...

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Main Authors:	Cheon, Jae Yeon, Mozersky, Jessica, Cook-Deegan, Robert
Format:	Online
Language:	English
Published:	BioMed Central 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4295298/

id	pubmed-4295298
recordtype	oai_dc
spelling	pubmed-42952982015-01-16 Variants of uncertain significance in BRCA: a harbinger of ethical and policy issues to come? Cheon, Jae Yeon Mozersky, Jessica Cook-Deegan, Robert Opinion After two decades of genetic testing and research, the BRCA1 and BRCA2 genes are two of the most well-characterized genes in the human genome. As a result, variants of uncertain significance (VUS; also called variants of unknown significance) are reported less frequently than for genes that have been less thoroughly studied. However, VUS continue to be uncovered, even for BRCA1/2. The increasing use of multi-gene panels and whole-genome and whole-exome sequencing will lead to higher rates of VUS detection because more genes are being tested, and most genomic loci have been far less intensively characterized than BRCA1/2. In this article, we draw attention to ethical and policy-related issues that will emerge. Experience garnered from BRCA1/2 testing is a useful introduction to the challenges of detecting VUS in other genetic testing contexts, while features unique to BRCA1/2 suggest key differences between the BRCA experience and the current challenges of multi-gene panels in clinical care. We propose lines of research and policy development, emphasizing the importance of pooling data into a centralized open-access database for the storage of gene variants to improve VUS interpretation. In addition, establishing ethical norms and regulated practices for sharing and curating data, analytical algorithms, interpretive frameworks and patient re-contact are important policy areas. BioMed Central 2014-12-19 /pmc/articles/PMC4295298/ /pubmed/25593598 http://dx.doi.org/10.1186/s13073-014-0121-3 Text en © Cheon et al.; licensee BioMed Central Ltd. 2014 The licensee has exclusive rights to distribute this article, in any medium, for 12 months following its publication. After this time, the article is available under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Cheon, Jae Yeon Mozersky, Jessica Cook-Deegan, Robert
spellingShingle	Cheon, Jae Yeon Mozersky, Jessica Cook-Deegan, Robert Variants of uncertain significance in BRCA: a harbinger of ethical and policy issues to come?
author_facet	Cheon, Jae Yeon Mozersky, Jessica Cook-Deegan, Robert
author_sort	Cheon, Jae Yeon
title	Variants of uncertain significance in BRCA: a harbinger of ethical and policy issues to come?
title_short	Variants of uncertain significance in BRCA: a harbinger of ethical and policy issues to come?
title_full	Variants of uncertain significance in BRCA: a harbinger of ethical and policy issues to come?
title_fullStr	Variants of uncertain significance in BRCA: a harbinger of ethical and policy issues to come?
title_full_unstemmed	Variants of uncertain significance in BRCA: a harbinger of ethical and policy issues to come?
title_sort	variants of uncertain significance in brca: a harbinger of ethical and policy issues to come?
description	After two decades of genetic testing and research, the BRCA1 and BRCA2 genes are two of the most well-characterized genes in the human genome. As a result, variants of uncertain significance (VUS; also called variants of unknown significance) are reported less frequently than for genes that have been less thoroughly studied. However, VUS continue to be uncovered, even for BRCA1/2. The increasing use of multi-gene panels and whole-genome and whole-exome sequencing will lead to higher rates of VUS detection because more genes are being tested, and most genomic loci have been far less intensively characterized than BRCA1/2. In this article, we draw attention to ethical and policy-related issues that will emerge. Experience garnered from BRCA1/2 testing is a useful introduction to the challenges of detecting VUS in other genetic testing contexts, while features unique to BRCA1/2 suggest key differences between the BRCA experience and the current challenges of multi-gene panels in clinical care. We propose lines of research and policy development, emphasizing the importance of pooling data into a centralized open-access database for the storage of gene variants to improve VUS interpretation. In addition, establishing ethical norms and regulated practices for sharing and curating data, analytical algorithms, interpretive frameworks and patient re-contact are important policy areas.
publisher	BioMed Central
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4295298/
_version_	1613176928950288384

Variants of uncertain significance in BRCA: a harbinger of ethical and policy issues to come?

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