Maetens Marion, Brown David, Irrthum Alexandre, Aftimos Philippe, Viale Giuseppe, Loibl Sibylle, Laes Jean-François, Campbell Peter J, Thompson Alastair, Cortes Javier, Seiler Sabine, Vinnicombe Sara, Oliveira Mafalda, Rothé Françoise, Bareche Yacine, Fumagalli Debora, Zardavas Dimitrios, Desmedt Christine, Piccart Martine, Loi Sherene, Sotiriou Christos
J.-C. Heuson Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
Breast International Group, Brussels, Belgium.
NPJ Breast Cancer. 2017 Jun 29;3:23. doi: 10.1038/s41523-017-0026-6. eCollection 2017.
Several studies have demonstrated the feasibility of molecular screening of tumour samples for matching patients with cancer to targeted therapies. However, most of them have been carried out at institutional or national level. Herein, we report on the pilot phase of AURORA (NCT02102165), a European multinational collaborative molecular screening initiative for advanced breast cancer patients. Forty-one patients were prospectively enroled at four participating centres across Europe. Metastatic tumours were biopsied and profiled using an Ion Torrent sequencing platform at a central facility. Sequencing results were obtained for 63% of the patients in real-time with variable turnaround time stemming from delays between patient consent and biopsy. At least one clinically actionable mutation was identified in 73% of patients. We used the Illumina sequencing technology for orthogonal validation and achieved an average of 66% concordance of substitution calls per patient. Additionally, copy number aberrations inferred from the Ion Torrent sequencing were compared to single nucleotide polymorphism arrays and found to be 59% concordant on average. Although this study demonstrates that powerful next generation genomic techniques are logistically ready for international molecular screening programs in routine clinical settings, technical challenges remain to be addressed in order to ensure the accuracy and clinical utility of the genomic data.
多项研究已证明对肿瘤样本进行分子筛查,以将癌症患者与靶向治疗相匹配的可行性。然而,其中大多数研究是在机构或国家层面开展的。在此,我们报告了AURORA(NCT02102165)的试点阶段,这是一项针对晚期乳腺癌患者的欧洲多国合作分子筛查倡议。41名患者在欧洲四个参与中心进行了前瞻性入组。对转移瘤进行活检,并在一个中央机构使用Ion Torrent测序平台进行分析。63%的患者实时获得了测序结果,周转时间因患者同意和活检之间的延迟而有所不同。73%的患者中至少鉴定出一种具有临床可操作性的突变。我们使用Illumina测序技术进行正交验证,每位患者的替换调用平均一致性达到66%。此外,将从Ion Torrent测序推断出的拷贝数变异与单核苷酸多态性阵列进行比较,发现平均一致性为59%。尽管这项研究表明强大的新一代基因组技术在后勤方面已为常规临床环境中的国际分子筛查项目做好准备,但仍有待解决技术挑战,以确保基因组数据的准确性和临床实用性。