Genetic features and application value of next generation sequencing in the diagnosis of synchronous multifocal lung adenocarcinoma

Chen,Xiaoyan; Lu,Jun; Wu,Yingying; Jiang,Xingran; Gu,Yajuan; Li,Yunlong; Zhao,Hongying; Jin,Mulan

doi:10.3892/ol.2020.11843

Genetic features and application value of next generation sequencing in the diagnosis of synchronous multifocal lung adenocarcinoma

Authors:
- Xiaoyan Chen
- Jun Lu
- Yingying Wu
- Xingran Jiang
- Yajuan Gu
- Yunlong Li
- Hongying Zhao
- Mulan Jin
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Affiliations: Department of Pathology, Capital Medical University, Affiliated Beijing Chaoyang Hospital, Beijing 100020, P.R. China
Published online on: July 9, 2020 https://doi.org/10.3892/ol.2020.11843
Pages: 2829-2839
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to elucidate the genetic features of multiple lung cancer (MLC) and identify effective molecular markers for diagnosis using next generation sequencing (NGS). The present data may also inform patient treatment and prognosis. A total of 35 lesions were obtained from 17 patients with MLC. Based on lesion histology and NGS, 13 cases of multiple primary lung cancer (MPLC) were identified and 4 cases were classified as intrapulmonary metastasis (IPM). All 4 patients with IPM exhibited an epidermal growth factor receptor (EGFR) mutation and synchronous mutation of at least one tumor suppressor gene. The frequency and percentage of EGFR mutations, accompanied with tumor suppressor genes, were significantly higher in patients with IPM compared with MPLC. Furthermore, a high EGFR‑heterogeneity score and male sex were risk factors of IPM occurrence. There were significant differences in mean EGFR mutation abundance alone, mutations of tumor suppressor genes and mutations of EGFR combined with tumor suppressor genes between patients with adenocarcinoma (ADC) and adenocarcinoma in situ (AIS). In conclusion, histological characteristics combined with genetic alterations may be an effective method for the diagnosis of MPLC and IPM, and NGS may serve as a useful diagnostic tool. MLC exhibited unique molecular characteristics, including higher rates of EGFR mutations, EGFR driver mutations accompanied with tumor suppressor gene mutations and the absence of anaplastic lymphoma kinase mutations, which may help distinguish between patients with MPLC or IPM. The present study hypothesized that the mean frequency of EGFR mutations, mutations of tumor suppressor genes and mutations of both EGFR and tumor suppressor genes may serve an important role in the development of AIS to ADC. The results of the present study highlight the potential underlying mechanisms of lung ADC development, which may assist with future elucidation of effective treatments to prevent the progression of lung cancer.

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