Moreno Fernando, Gayarre Javier, López-Tarruella Sara, Del Monte-Millán María, Picornell Antonio C, Álvarez Enrique, García-Saenz José Ángel, Jerez Yolanda, Márquez-Rodas Iván, Echavarría Isabel, Palomero Maribel, Bueno Coralia, Aragón Bodí Ana María, Muñoz Marta Sanchez, González Del Val Ricardo, Bueno Oscar, Cebollero-Presmanes María, Ocaña Inmaculada, Arias Ainhoa, Romero Paula, Massarrah Tatiana, Ramos-Medina Rocío, Martín Miguel
Centro de Investigación Biomédica en Red Cáncer, Madrid, Spain.
Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
JCO Precis Oncol. 2019 Dec;3:1-16. doi: 10.1200/PO.18.00263.
Genetic heterogeneity between primary tumors and their metastatic lesions has been documented in several breast cancer studies. However, the selection of therapy for patients with metastatic breast cancer and the search for biomarkers for targeted therapy are often based on findings from the primary tumor, mainly because of the difficulty of distant metastasis core biopsies. New methods for monitoring genomic changes in metastatic breast cancer are needed (ie, circulating tumor DNA [ctDNA] genomic analysis). The objectives of this study were to assess the concordance of genomic variants between primary and metastatic tumor tissues and the sensitivity of plasma ctDNA analysis to identify variants detected in tumor biopsies.
Next-generation sequencing technology was used to assess the genomic mutation profile of a panel of 54 cancer genes in matched samples of primary tumor, metastatic tumor, and plasma from 40 patients with metastatic breast cancer.
Using Ion Torrent technology (ThermoFisher Scientific, Waltham, MA), we identified 110 variants that were common to the primary and metastatic tumors. ctDNA analysis had a sensitivity of 0.972 in detecting variants present in both primary and metastatic tissues. In addition, we identified 13 variants in metastatic tissue and ctDNA not present in primary tumor.
We identified genomic variants present in metastatic biopsies and plasma ctDNA that were not present in the primary tumor. Deep sequencing of plasma ctDNA detected most DNA variants previously identified in matched primary and metastatic tissues. ctDNA might aid in therapy selection and in the search for biomarkers for drug development in metastatic breast cancer.
在多项乳腺癌研究中已证实原发性肿瘤与其转移病灶之间存在基因异质性。然而，转移性乳腺癌患者的治疗选择以及靶向治疗生物标志物的寻找通常基于原发性肿瘤的研究结果，主要是因为获取远处转移灶的核心活检样本存在困难。因此需要新的方法来监测转移性乳腺癌的基因组变化（即循环肿瘤DNA[ctDNA]基因组分析）。本研究的目的是评估原发性和转移性肿瘤组织之间基因组变异的一致性，以及血浆ctDNA分析识别肿瘤活检中检测到的变异的敏感性。
采用新一代测序技术评估40例转移性乳腺癌患者的原发性肿瘤、转移性肿瘤及血浆匹配样本中54个癌症基因组成的基因panel的基因突变谱。
使用Ion Torrent技术（赛默飞世尔科技公司生产，马萨诸塞州沃尔瑟姆市），我们鉴定出原发性和转移性肿瘤共有的110个变异。ctDNA分析检测原发性和转移性组织中均存在的变异的敏感性为0.972。此外，我们在转移性组织和ctDNA中鉴定出13个原发性肿瘤中不存在的变异。
我们在转移性活检组织和血浆ctDNA中鉴定出原发性肿瘤中不存在的基因组变异。血浆ctDNA的深度测序检测到了先前在匹配的原发性和转移性组织中鉴定出的大多数DNA变异。ctDNA可能有助于转移性乳腺癌的治疗选择以及寻找药物开发的生物标志物。
