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

Davidson, AL; Dressel, U; Norris, S; Canson, DM; Glubb, DM; Fortuno, C; Hollway, GE; Parsons, MT; Vidgen, ME; Holmes, O; Koufariotis, LT; Lakis, V; Leonard, C; Wood, S; Xu, Q; McCart Reed, AE; Pickett, HA; Al-Shinnag, MK; Austin, RL; Burke, J; Cops, EJ; Nichols, CB; Goodwin, A; Harris, MT; Higgins, MJ; Ip, EL; Kiraly-Borri, C; Lau, C; Mansour, JL; Millward, MW; Monnik, MJ; Pachter, NS; Ragunathan, A; Susman, RD; Townshend, SL; Trainer, AH; Troth, SL; Tucker, KM; Wallis, MJ; Walsh, M; Williams, RA; Winship, IM; Newell, F; Tudini, E; Pearson, JV; Poplawski, NK; Mar Fan, HG; James, PA; Spurdle, AB; Waddell, N; Ward, RL

Author(s): Davidson, AL; Dressel, U; Norris, S; Canson, DM; Glubb, DM; Fortuno, C; Hollway, GE; Parsons, MT; Vidgen, ME; Holmes, O; Koufariotis, LT; Lakis, V; Leonard, C; Wood, S; Xu, Q; McCart Reed, AE; Pickett, HA; Al-Shinnag, MK; Austin, RL; Burke, J; Cops, EJ; Nichols, CB; Goodwin, A; Harris, MT; Higgins, MJ; Ip, EL; Kiraly-Borri, C; Lau, C; Mansour, JL; Millward, MW; Monnik, MJ; Pachter, NS; Ragunathan, A; Susman, RD; Townshend, SL; Trainer, AH; Troth, SL; Tucker, KM; Wallis, MJ; Walsh, M; Williams, RA; Winship, IM; Newell, F; Tudini, E; Pearson, JV; Poplawski, NK; Mar Fan, HG; James, PA; Spurdle, AB; Waddell, N; Ward, RL;
Details: Publication Year 2023-09-19,Volume 15,Issue #1,Page 74
Journal Title: Genome Medicine
Publication Type: Research article
Abstract: 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.
Publisher: BioMed Central
Keywords: Humans; Prospective Studies; *Neoplastic Syndromes, Hereditary; Oncogenes; Genetic Testing; Germ Cells; Diagnostic testing; Familial cancer; Genetics; Health economics; Variants; Whole-genome sequencing
Department(s): Familial Cancer Centre
PubMed ID: 37723522
Publisher's Version: https://doi.org/10.1186/s13073-023-01223-1
Open Access at Publisher's Site: https://doi.org/10.1186/s13073-023-01223-1
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2023-11-14 03:57:58

Last Modified: 2023-11-14 03:58:49