Universität zu Köln

Eccles, D. M., Mitchell, G., Monteiro, A. N. A., Schmutzler, R., Couch, F. J., Spurdle, A. B. and Gomez-Garcia, E. B. (2015). BRCA1 and BRCA2 genetic testing-pitfalls and recommendations for managing variants of uncertain clinical significance. Ann. Oncol., 26 (10). S. 2057 - 2066. OXFORD: OXFORD UNIV PRESS. ISSN 1569-8041

Full text not available from this repository.

Abstract

Background: 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. Design: 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. Results and conclusion: 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Eccles, D. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mitchell, G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Monteiro, A. N. A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmutzler, R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Couch, F. J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Spurdle, A. B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gomez-Garcia, E. B. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-391230
DOI:	10.1093/annonc/mdv278
Journal or Publication Title:	Ann. Oncol.
Volume:	26
Number:	10
Page Range:	S. 2057 - 2066
Date:	2015
Publisher:	OXFORD UNIV PRESS
Place of Publication:	OXFORD
ISSN:	1569-8041
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DNA-SEQUENCE VARIANTS; OVARIAN-CANCER; MISSENSE SUBSTITUTIONS; HEREDITARY BREAST; CLASSIFICATION; MUTATION; IMPACT; BREAST/OVARIAN; SUSCEPTIBILITY; PATHOGENICITY Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/39123