Towards controlled terminology for reporting germline cancer susceptibility variants: an ENIGMA report
Year: 2019
Type: article
Abstract: The vocabulary currently used to describe genetic variants and their consequences reflects many years of studying and discovering monogenic disease with high penetrance. With the recent rapid expansion of genetic testing brought about by wide availability of high-throughput massively parallel sequencing platforms, accurate variant interpretation has become a major issue. The vocabulary used to describe single genetic variants in silico, in vitro, in vivo and as a contributor to human disease uses terms in common, but the meaning is not necessarily shared across all these contexts. In the setting of cancer genetic tests, the added dimension of using data from genetic sequencing of tumour DNA to direct treatment is an additional source of confusion to those who are not experienced in cancer genetics. The language used to describe variants identified in cancer susceptibility genetic testing typically still reflects an outdated paradigm of Mendelian inheritance with dichotomous outcomes. Cancer is a common disease with complex genetic architecture; an improved lexicon is required to better communicate among scientists, clinicians and patients, the risks and implications of genetic variants detected. This review arises from a recognition of, and discussion about, inconsistencies in vocabulary usage by members of the ENIGMA international multidisciplinary consortium focused on variant classification in breast-ovarian cancer susceptibility genes. It sets out the vocabulary commonly used in genetic variant interpretation and reporting, and suggests a framework for a common vocabulary that may facilitate understanding and clarity in clinical reporting of germline genetic tests for cancer susceptibility.
Source: Journal of Medical Genetics
Authors: Amanda B Spurdle, Stephanie Greville-Heygate, Antonis C Antoniou, Melissa Brown, Leslie Burke, Miguel de la Hoya, Susan Domchek, Thilo Dörk, Helen V Firth, Alvaro N Monteiro, Arjen Mensenkamp, Michael T Parsons, Paolo Radice, Mark Robson, Marc Tischkowitz, Emma Tudini, Clare Turnbull, Maaike PG Vreeswijk, Logan C Walker, Sean Tavtigian, Diana M Eccles
Institutions: QIMR Berghofer Medical Research Institute, University of Southampton, University of Cambridge, The University of Queensland, Hospital Clínico San Carlos, Abramson Cancer Center, University of Pennsylvania, Medizinische Hochschule Hannover, Cambridge University Hospitals NHS Foundation Trust, Moffitt Cancer Center, Radboud University Medical Center, Fondazione IRCCS Istituto Nazionale dei Tumori, Memorial Sloan Kettering Cancer Center, Institute of Cancer Research, William Harvey Research Institute, Leiden University Medical Center, University of Otago, University of Utah, Huntsman Cancer Institute
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
Funders: Breast Cancer Research Foundation, Cancer Research UK, European Commission, Royal Society Te Apārangi, Associazione Italiana per la Ricerca sul Cancro, National Institutes of Health, Medical Research Council, National Health and Medical Research Council, Cancer Council Queensland, Instituto de Salud Carlos III, National Cancer Institute
Awards: G2004299919, G2264006398, G2437083349, Caracterización Molecular de un Exoma FA/BRCA/HR con Anotaciones de Relevancia Clínica, G3602505857, Breast Cancer Risk after Diagnostic Gene Sequencing (BRIDGES), G3978591521, G4014780978, G4102770861, G434337789, G4409261390, G4970236007, G6402876381, G6871046858, G7381565345, G782458776, Clinical classification of regulatory variants in breast cancer susceptibility genes, Research Fellowship – Genetic Epidemiology studies of hormonal cancers to inform improved healthcare, G9000003249, Cancer Center Support Grant, G911686871
OpenAlex ID: W2939627968