Bieg-Bourne Cheyennedra C, Millis Sherri Z, Piccioni David E, Fanta Paul T, Goldberg Michael E, Chmielecki Juliann, Parker Barbara A, Kurzrock Razelle
San Diego State University, San Diego, California.
Center for Personalized Cancer Therapy and Division of Hematology and Oncology, UC San Diego Moores Cancer Center, La Jolla, California.
Cancer Res. 2017 Nov 15;77(22):6313-6320. doi: 10.1158/0008-5472.CAN-17-1569. Epub 2017 Sep 22.
Enhancements in clinical-grade next-generation sequencing (NGS) have fueled the advancement of precision medicine in the clinical oncology field. Here, we survey the molecular profiles of 1,113 patients with diverse malignancies who successfully underwent clinical-grade NGS (236-404 genes) in an academic tertiary cancer center. Among the individual tumors examined, the majority showed at least one detectable alteration (97.2%). Among 2,045 molecular aberrations was the involvement of 302 distinct genes. The most commonly altered genes were (47.0%), (18.0%), (17.0%), and (16.0%), and the majority of patients had tumors that harbored multiple alterations. Tumors displayed a median of four alterations (range, 0-29). Most individuals had at least one potentially actionable alteration (94.7%), with the median number of potentially actionable alterations per patient being 2 (range, 0-13). A total of 1,048 (94.2%) patients exhibited a unique molecular profile, with either genes altered or loci within the gene(s) altered being distinct. Approximately 13% of patients displayed a genomic profile identical to at least one other patient; although genes altered were the same, the affected loci may have differed. Overall, our results underscore the complex heterogeneity of malignancies and argue that customized combination therapies will be essential to optimize cancer treatment regimens. .
临床级下一代测序(NGS)技术的进步推动了临床肿瘤学领域精准医学的发展。在此,我们调查了在一家学术性三级癌症中心成功接受临床级NGS(检测236 - 404个基因)的1113例不同恶性肿瘤患者的分子特征。在所检测的个体肿瘤中,大多数至少显示出一种可检测到的改变(97.2%)。在2045个分子异常中涉及302个不同的基因。最常发生改变的基因是(47.0%)、(18.0%)、(17.0%)和(16.0%),并且大多数患者的肿瘤存在多种改变。肿瘤显示的改变中位数为4种(范围为0 - 29种)。大多数个体至少有一个潜在可靶向治疗的改变(94.7%),每位患者潜在可靶向治疗改变的中位数为2种(范围为0 - 13种)。共有1048例(94.2%)患者表现出独特的分子特征,即改变的基因或基因内改变的位点不同。约13%的患者显示出与至少一名其他患者相同的基因组特征;尽管改变的基因相同,但受影响的位点可能不同。总体而言,我们的结果强调了恶性肿瘤复杂的异质性,并表明定制的联合疗法对于优化癌症治疗方案至关重要。