Wong S Q, Fellowes A, Doig K, Ellul J, Bosma T J, Irwin D, Vedururu R, Tan A Y-C, Weiss J, Chan K S, Lucas M, Thomas D M, Dobrovic A, Parisot J P, Fox S B
1] Department of Pathology, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia [2] Division of Cancer Research, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Victoria 3002, Australia.
Department of Pathology, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia.
Br J Cancer. 2015 Apr 14;112(8):1411-20. doi: 10.1038/bjc.2015.80. Epub 2015 Mar 5.
Recent discoveries in cancer research have revealed a plethora of clinically actionable mutations that provide therapeutic, prognostic and predictive benefit to patients. The feasibility of screening mutations as part of the routine clinical care of patients remains relatively unexplored as the demonstration of massively parallel sequencing (MPS) of tumours in the general population is required to assess its value towards the health-care system.
Cancer 2015 study is a large-scale, prospective, multisite cohort of newly diagnosed cancer patients from Victoria, Australia with 1094 patients recruited. MPS was performed using the Illumina TruSeq Amplicon Cancer Panel.
Overall, 854 patients were successfully sequenced for 48 common cancer genes. Accurate determination of clinically relevant mutations was possible including in less characterised cancer types; however, technical limitations including formalin-induced sequencing artefacts were uncovered. Applying strict filtering criteria, clinically relevant mutations were identified in 63% of patients, with 26% of patients displaying a mutation with therapeutic implications. A subset of patients was validated for canonical mutations using the Agena Bioscience MassARRAY system with 100% concordance. Whereas the prevalence of mutations was consistent with other institutionally based series for some tumour streams (breast carcinoma and colorectal adenocarcinoma), others were different (lung adenocarcinoma and head and neck squamous cell carcinoma), which has significant implications for health economic modelling of particular targeted agents. Actionable mutations in tumours not usually thought to harbour such genetic changes were also identified.
Reliable delivery of a diagnostic assay able to screen for a range of actionable mutations in this cohort was achieved, opening unexpected avenues for investigation and treatment of cancer patients.
癌症研究中的最新发现揭示了大量具有临床可操作性的突变，这些突变为患者提供了治疗、预后和预测方面的益处。作为患者常规临床护理的一部分，筛查突变的可行性仍有待进一步探索，因为需要在普通人群中对肿瘤进行大规模平行测序（MPS），以评估其对医疗保健系统的价值。
“癌症2015研究”是一项大规模、前瞻性、多中心队列研究，招募了来自澳大利亚维多利亚州的1094例新诊断癌症患者。使用Illumina TruSeq Amplicon癌症检测板进行MPS。
总体而言，854例患者成功对48个常见癌症基因进行了测序。能够准确确定临床相关突变，包括在特征较少的癌症类型中；然而，也发现了技术局限性，包括福尔马林诱导的测序假象。应用严格的筛选标准，在63%的患者中鉴定出临床相关突变，26%的患者显示出具有治疗意义的突变。使用Agena Bioscience MassARRAY系统对一部分患者的典型突变进行了验证，一致性为100%。虽然某些肿瘤类型（乳腺癌和结直肠癌）的突变发生率与其他基于机构的系列研究一致，但其他肿瘤类型（肺腺癌和头颈部鳞状细胞癌）则不同，这对特定靶向药物的健康经济模型具有重要意义。在通常不被认为存在此类基因变化的肿瘤中也发现了可操作的突变。
在该队列中实现了可靠的诊断检测，能够筛查一系列可操作的突变，为癌症患者的调查和治疗开辟了意想不到的途径。
