Department of Clinical Biochemistry, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark.
Department of Oncology, Aarhus University Hospital, Norrebrogade 44 bld. 5, 8000, Aarhus C, Denmark.
BMC Cancer. 2018 Feb 15;18(1):191. doi: 10.1186/s12885-018-4108-0.
Lung cancer patients with an activating mutation in the EGFR (epidermal growth factor receptor) can develop resistance to erlotinib treatment, which is often mediated by the T790M resistance mutation in EGFR. The difficulties in obtaining biopsies at progression make it challenging to investigate the appearance of the T790M mutation at progression in large patient cohorts. We have used cell free DNA (cfDNA) from patients treated with erlotinib to investigate if the development of a T790M mutation coincides with the presence of an activating EGFR mutation in the pre-treatment blood sample.
A cohort of 227 NSCLC (non-small cell lung cancer) adenocarcinoma patients was treated with erlotinib irrespective of EGFR-mutational status. Blood samples were drawn immediately before erlotinib treatment was initiated and again at progression. The cobas® EGFR Mutation Test v2 designed for cfDNA was used to identify 42 EGFR mutations.
Of the 227 NSCLC patients, blood samples were available from 144 patients both before erlotinib treatment and at progression (within 1 month before or after clinical progression). One hundred and twenty-eight of the 144 were wild-type EGFR before treatment, and we demonstrate that the T790M mutation was not present at progression in any of these. In contrast, in the 16 patients with an activating EGFR mutation in the pre-treatment blood sample six patients (38%) were identified with a T790M mutation in the progression blood sample.
The T790M resistance mutation is only found in the cfDNA of erlotinib-treated NSCLC patients if they have an activating EGFR mutation before treatment.
表皮生长因子受体（EGFR）激活突变的肺癌患者对厄洛替尼治疗会产生耐药，这种耐药通常由 EGFR 中的 T790M 耐药突变介导。进展时获取活检存在困难，这使得在大型患者队列中研究进展时 T790M 突变的出现变得具有挑战性。我们已经使用接受厄洛替尼治疗的患者的无细胞 DNA（cfDNA）来研究 T790M 突变的发展是否与治疗前血液样本中存在激活的 EGFR 突变同时发生。
一组 227 例非小细胞肺癌（NSCLC）腺癌患者接受了厄洛替尼治疗，无论 EGFR 突变状态如何。在开始厄洛替尼治疗之前和进展时立即抽取血液样本。使用设计用于 cfDNA 的 cobas® EGFR Mutation Test v2 来鉴定 42 种 EGFR 突变。
在 227 例 NSCLC 患者中，144 例患者的血液样本在厄洛替尼治疗前和进展时（在临床进展前 1 个月内）都可用。144 例患者中有 128 例在治疗前为野生型 EGFR，我们证明在这些患者中没有在进展时存在 T790M 突变。相比之下，在治疗前血液样本中存在激活的 EGFR 突变的 16 例患者中，有 6 例（38%）在进展时血液样本中检测到 T790M 突变。
只有在治疗前存在激活的 EGFR 突变的接受厄洛替尼治疗的 NSCLC 患者的 cfDNA 中才会发现 T790M 耐药突变。
