癌症易感性变异的全基因组测序的临床效用和成本——一项多中心前瞻队列研究。
The clinical utility and costs of whole-genome sequencing to detect cancer susceptibility variants-a multi-site prospective cohort study.
发表日期：2023 Sep 19
作者：
Aimee L Davidson, Uwe Dressel, Sarah Norris, Daffodil M Canson, Dylan M Glubb, Cristina Fortuno, Georgina E Hollway, Michael T Parsons, Miranda E Vidgen, Oliver Holmes, Lambros T Koufariotis, Vanessa Lakis, Conrad Leonard, Scott Wood, Qinying Xu, Amy E McCart Reed, Hilda A Pickett, Mohammad K Al-Shinnag, Rachel L Austin, Jo Burke, Elisa J Cops, Cassandra B Nichols, Annabel Goodwin, Marion T Harris, Megan J Higgins, Emilia L Ip, Catherine Kiraly-Borri, Chiyan Lau, Julia L Mansour, Michael W Millward, Melissa J Monnik, Nicholas S Pachter, Abiramy Ragunathan, Rachel D Susman, Sharron L Townshend, Alison H Trainer, Simon L Troth, Katherine M Tucker, Mathew J Wallis, Maie Walsh, Rachel A Williams, Ingrid M Winship, Felicity Newell, Emma Tudini, John V Pearson, Nicola K Poplawski, Helen G Mar Fan, Paul A James, Amanda B Spurdle, Nicola Waddell, Robyn L Ward
来源：
GENES & DEVELOPMENT
摘要：
许多家庭和个人不符合已知的遗传性癌症综合征的诊断标准，但显示出异常的癌症聚集现象。 这些家族可能携带癌症易感基因的病理变异，并具有较高的癌症发生风险。这项多中心前瞻性研究招募了195名患有癌症的参与者，他们被怀疑患有遗传性癌症综合征，之前的临床靶向基因检测要么没有提供有用信息，要么不可用。为了确定解释参与者病情的病理致病变异，进行了遗传全基因组测序（WGS）和全面的癌症虚拟基因组分析。发现与出现的癌症一致的致病变异在5.1%（10/195）的参与者中被确定，并且另外9.7%（19/195）的参与者中发现了被认为是次要发现的具有潜在风险管理意义的致病变异。健康经济学分析估计，对于带有可操作变异的每个病例，使用虚拟基因组的前期WGS的边际成本显著低于标准检测后进行WGS（$8744澳元与$24,894澳元）。财务分析表明，与传统检测相比，全国采用诊断性WGS检测将需要政府年度支出的九倍增加。这些发现证明了使用WGS代替传统检测可为癌症患者和家庭提供临床重要的益处的理由。采用这种方法将取决于不同付款方对可负担性的看法。© 2023. Springer Nature旗下BioMed Central Ltd.
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.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.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.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.© 2023. BioMed Central Ltd., part of Springer Nature.