Implementing gene curation for hereditary cancer susceptibility in Australia: achieving consensus on genes with clinical utility

• Published in: Journal of medical genetics Vol. 58; no. 12; pp. 853 - 858
• Main Authors: Tudini, Emma, Davidson, Aimee L, Dressel, Uwe, Andrews, Lesley, Antill, Yoland, Crook, Ashley, Field, Michael, Gattas, Michael, Harris, Rebecca, Kirk, Judy, Pachter, Nicholas, Salmon, Lucinda, Susman, Rachel, Townshend, Sharron, Trainer, Alison H, Tucker, Katherine M, Mitchell, Gillian, James, Paul A, Ward, Robyn L, Mar Fan, Helen, Poplawski, Nicola K, Spurdle, Amanda B
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd 01.12.2021; BMJ Publishing Group LTD
• Subjects: Australia; Cancer; Clinical decision making; Clinical guidelines; Clinical medicine; Clinics; Collaboration; Consensus; Family Health; Female; Genes; Genetic Association Studies - methods; genetic counseling; Genetic Counseling - methods; genetic predisposition to disease; Genetic Predisposition to Disease - genetics; genetic testing; Genetic Testing - methods; Genetics; Genomes; Genomics; Genotype & phenotype; Germ-Line Mutation; Humans; Male; Medical Oncology - methods; Medical research; Molecular Sequence Annotation - methods; Neoplasms - diagnosis; Neoplasms - genetics; Patients; Pediatrics; Pedigree; Phenotypes; Polls & surveys; Testing laboratories; Tumor Suppressor Proteins - genetics; Tumors; Australia; New Zealand; United Kingdom > UK; genetic counseling; clinical decision-making; genetic predisposition to disease; genetic testing
• ISSN: 0022-2593; 1468-6244
• DOI: 10.1136/jmedgenet-2020-107140

BackgroundThe strength of evidence supporting the validity of gene-disease relationships is variable. Hereditary cancer has the additional complexity of low or moderate penetrance for some confirmed disease-associated alleles.MethodsTo promote national consistency in interpretation of hereditary cancer/tumour gene test results, we requested opinions of representatives from Australian Family Cancer Clinics regarding the clinical utility of 157 genes initially collated for a national research project. Viewpoints were sought by initial survey, face-to-face workshop and follow-up survey. Subsequent review was undertaken by the eviQ Cancer Genetics Reference Committee, a national resource providing evidence-based and consensus-driven cancer treatment protocols.ResultsGenes were categorised by clinical actionability as: relevant for testing on presentation of common cancer/tumour types (n=45); relevant for testing in the context of specific rare phenotypes (n=74); insufficient clinical utility (n=34) or contentious clinical utility (n=3). Opinions for several genes altered during the study time frame, due to new information.ConclusionThrough an iterative process, consensus was achieved on genes with clinical utility for hereditary cancer/tumour conditions in the Australian setting. This study highlighted need for regular review of gene-disease lists, a role assumed in Australia for hereditary cancer/tumour predisposition genes by the eviQ Cancer Genetics Reference Committee.