Nardo Giorgia, Carlet Jessica, Marra Ludovica, Bonanno Laura, Boscolo Alice, Dal Maso Alessandro, Boscolo Bragadin Andrea, Indraccolo Stefano, Zulato Elisabetta
Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV - IRCCS, Padova, Italy.
Medical Oncology 2, Istituto Oncologico Veneto IOV - IRCCS, Padova, Italy.
Front Oncol. 2021 Jan 15;10:607840. doi: 10.3389/fonc.2020.607840. eCollection 2020.
Molecular profiling of advanced mutated NSCLC has recently demonstrated the co-existence of multiple genetic alterations. Specifically, co-existing -mutations in NSCLCs have been described, despite their prevalence at progression and their role in the response to tyrosine kinase inhibitors (TKIs) remain marginally explored. Aim of our study was to investigate the prevalence of co-existing mutations at the time of progressive disease and explore their impact on clinical outcome.
We retrospectively analyzed by digital droplet PCR prevalence of co-mutations in 106 plasma samples of mutated NSCLC patients, in progressive disease after TKI treatment as first-line therapy.
co-mutations (codon 12 and 13) were identified in 3 patients (2.8% of analyzed samples), with low allelic frequency (<0.2%), and had a negative impact on clinical outcome to first-line TKI.
Detection of mutations in cell-free DNA of mutant NSCLC patients at progression after first or second generation TKI is a rare event. Due to their low abundance, the negative impact of mutations on the response to TKI remains to be confirmed in larger studies.
晚期突变型非小细胞肺癌（NSCLC）的分子谱分析最近显示存在多种基因改变。具体而言，已描述了非小细胞肺癌中共存的-突变，尽管其在疾病进展时的发生率及其在对酪氨酸激酶抑制剂（TKIs）反应中的作用仍未得到充分研究。我们研究的目的是调查疾病进展时共存突变的发生率，并探讨它们对临床结局的影响。
我们通过数字液滴PCR回顾性分析了106例突变型NSCLC患者血浆样本中-共突变的发生率，这些患者在接受TKI治疗作为一线治疗后出现疾病进展。
在3例患者（占分析样本的2.8%）中鉴定出共突变（密码子12和13），等位基因频率较低（<0.2%），并且对一线TKI的临床结局有负面影响。
在第一代或第二代TKI治疗后进展的突变型NSCLC患者的游离DNA中检测到突变是罕见事件。由于其丰度较低，突变对TKI反应的负面影响仍有待在更大规模的研究中得到证实。
