The clinical utility and costs of whole-genome sequencing to detect cancer susceptibility variants—a multi-site prospective cohort study

Background Many families and individuals do not meet criteria for a known hereditary cancer syndrome but display unusual clusters of cancers. These families may carry pathogenic variants in cancer predisposition genes and be at higher risk for developing cancer. Methods This multi-centre prospective...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Genome medicine Jg. 15; H. 1; S. 1 - 16
Hauptverfasser: Davidson, Aimee L., Dressel, Uwe, Norris, Sarah, Canson, Daffodil M., Glubb, Dylan M., Fortuno, Cristina, Hollway, Georgina E., Parsons, Michael T., Vidgen, Miranda E., Holmes, Oliver, Koufariotis, Lambros T., Lakis, Vanessa, Leonard, Conrad, Wood, Scott, Xu, Qinying, McCart Reed, Amy E., Pickett, Hilda A., Al-Shinnag, Mohammad K., Austin, Rachel L., Burke, Jo, Cops, Elisa J., Nichols, Cassandra B., Goodwin, Annabel, Harris, Marion T., Higgins, Megan J., Ip, Emilia L., Kiraly-Borri, Catherine, Lau, Chiyan, Mansour, Julia L., Millward, Michael W., Monnik, Melissa J., Pachter, Nicholas S., Ragunathan, Abiramy, Susman, Rachel D., Townshend, Sharron L., Trainer, Alison H., Troth, Simon L., Tucker, Katherine M., Wallis, Mathew J., Walsh, Maie, Williams, Rachel A., Winship, Ingrid M., Newell, Felicity, Tudini, Emma, Pearson, John V., Poplawski, Nicola K., Mar Fan, Helen G., James, Paul A., Spurdle, Amanda B., Waddell, Nicola, Ward, Robyn L.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London BioMed Central 19.09.2023
BioMed Central Ltd
Springer Nature B.V
BMC
Schlagworte:
Bioinformatics
Biomedical and Life Sciences
Biomedicine
Cancer
Cancer Research
Cohort analysis
Datasets
Development and progression
Diagnosis
Diagnostic testing
Disease susceptibility
DNA sequencing
Economic analysis
Familial cancer
Financial analysis
Gene loci
Genetic aspects
Genetic research
Genetic screening
Genetic testing
Genetics
Genomes
Genomics
Genotype & phenotype
Health economics
Human Genetics
Medical research
Medicine/Public Health
Melanoma
Metabolomics
Nucleotide sequencing
Oncology, Experimental
Systems Biology
Variants
Whole genome sequencing
Australia
Variants
Diagnostic testing
Familial cancer
Genetics
Health economics
Whole-genome sequencing
ISSN:1756-994X, 1756-994X
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Background Many families and individuals do not meet criteria for a known hereditary cancer syndrome but display unusual clusters of cancers. These families may carry pathogenic variants in cancer predisposition genes and be at higher risk for developing cancer. Methods This multi-centre prospective study recruited 195 cancer-affected participants suspected to have a hereditary cancer syndrome for whom previous clinical targeted genetic testing was either not informative or not available. To identify pathogenic disease-causing variants explaining participant presentation, germline whole-genome sequencing (WGS) and a comprehensive cancer virtual gene panel analysis were undertaken. Results Pathogenic variants consistent with the presenting cancer(s) were identified in 5.1% (10/195) of participants and pathogenic variants considered secondary findings with potential risk management implications were identified in another 9.7% (19/195) of participants. Health economic analysis estimated the marginal cost per case with an actionable variant was significantly lower for upfront WGS with virtual panel ($8744AUD) compared to standard testing followed by WGS ($24,894AUD). Financial analysis suggests that national adoption of diagnostic WGS testing would require a ninefold increase in government annual expenditure compared to conventional testing. Conclusions These findings make a case for replacing conventional testing with WGS to deliver clinically important benefits for cancer patients and families. The uptake of such an approach will depend on the perspectives of different payers on affordability.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
ISSN:1756-994X
1756-994X
DOI:10.1186/s13073-023-01223-1