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Cancer Biol Ther. 2019;20(8):1097-1104. doi: 10.1080/15384047.2019.1595280. Epub 2019 Apr 16.

The in cis compound EGFR mutations in Chinese advanced non-small cell lung cancer patients.

Author information

1
a Department of Respiratory Medicine , Center for Molecular Medicine, Xiangya Hospital , Central South University , Changsha , China.
2
b Department of Respiratory Medicine, First Affiliated Hospital , Guangzhou Medical University , Guangzhou , China.
3
c Guangdong Lung Cancer Institute , Guangzhou , China.
4
d Shanghai Lung Cancer Center, Shanghai Chest Hospital , Shanghai Jiao Tong University , Shanghai , China.
5
e Department of Oncology, Shanghai Pulmonary Hospital , Tongji University Medical School , Shanghai , China.
6
f Department of Respiratory Medicine , Zhongshan Hospital, Fudan University , Shanghai , China.
7
g Zhejiang Cancer Hospital , Hangzhou , China.
8
h Department of Oncology, West China Hospital , Sichuan University , Chengdu , China.
9
i First Affiliated Hospital , Nanjing Medical University , Nanjing , China.
10
j First Affiliated Hospital , Zhengzhou University , Zhengzhou , China.
11
k Burning Rock Biotech , Guangzhou , China.

Abstract

Literatures regarding the prevalence and clinical significance of compound EGFR mutations are limited. Until now, none of retrospective or prospective research has focused on in cis compound EGFR mutations except case reports. In this study, we screened a cohort of 3,000 treatment-naïve Chinese advanced NSCLC patients using capture-based ultra-deep targeted sequencing to evaluate the prevalence of EGFR in cis compound mutations and the efficacy of EGFR-TKI in this population. Of the 3,000 patients screened, 1,266 (42.2%) had EGFR mutation; among them, 15 patients (1.2%) harboring in cis compound EGFR mutations, with 10 patients carrying EGFR L858R in combination with a rare mutation and five patients carrying two rare EGFR mutations. No patient with EGFR 19del was observed. Interestingly, no in trans configuration was identified in this cohort. All of the patients harboring in cis compound EGFR mutations were non-smokers, histologically diagnosed with adenocarcinoma and received first-generation EGFR-TKI. Furthermore, our data also revealed that patients with in cis compound EGFR mutations exhibit comparable PFS to first generation EGFR-TKI comparing to patients with single activating EGFR mutation. This observation was further supported by in silico molecular modeling analyses which demonstrated in cis compound mutations do not alter the ATP-binding pocket of EGFR, thus having no effect on the interaction between gefitinib and EGFR.

KEYWORDS:

Chinese; EGFR; In cis; compound mutations; non-small cell lung cancer

PMID:
30990107
PMCID:
PMC6605978
[Available on 2020-04-16]
DOI:
10.1080/15384047.2019.1595280

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