AUTHOR=Pei Guotian , Li Mingwei , Min Xianjun , Liu Qiang , Li Dasheng , Yang Yingshun , Wang Shuai , Wang Xiaoyu , Wang Huina , Cheng Huanqing , Cao Shanbo , Huang Yuqing 

TITLE=Molecular Identification and Genetic Characterization of Early-Stage Multiple Primary Lung Cancer by Large-Panel Next-Generation Sequencing Analysis

JOURNAL=Frontiers in Oncology

VOLUME=Volume 11 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.653988

DOI=10.3389/fonc.2021.653988

ISSN=2234-943X

ABSTRACT=Objective: The incidence of early-stage multiple primary lung cancer (MPLC) has been increasing in recent years, while the ideal strategy for its diagnosis and treatment remains controversial. The present study conducted genomic analysis to identify a new molecular classification method for accurately predicting the diagnosis and therapy for patients with early-stage MPLC.
Methods: A total of 240 tissue samples from 203 patients with multiple-non-small-cell lung cancers (NSCLC) (n = 30), early-stage single-NSCLC (Group A, n = 94), and advanced-stage NSCLC (Group B, n = 79) were subjected to targeted multigene panel sequencing.
Results: Thirty patients for whom next-generation sequencing was performed on >1 tumour were identified, yielding 45 tumour pairs. The frequencies of EGFR, TP53, RBM10, ERBB2, and CDKN2A mutations exhibited significant differences between early- and advanced-stage NSCLC. The prevalence of the EGFR L858R mutation in early-stage NSCLC was remarkably higher than that in advanced-stage NSCLC (P = 0.047). The molecular method classified tumour pairs into 26 definite MPLC tumours and 4 intrapulmonary metastasis (IM) tumours. A high rate of discordance in driver genetic alterations was found in the different tumour lesions of MPLC patients. The prospective Martini histologic prediction of MPLC was discordant with the molecular method for 3 patients (16.7%), particularly in the prediction of IM (91.7% discordant).
Conclusions: Comprehensive molecular evaluation allows the unambiguous delineation of clonal relationships among tumours. In comparison, the Martini and Melamed criteria have notable limitations in the recognition of IM. Our results support the adoption of a large panel to supplement histology for strongly discriminating NSCLC clonal relationships in clinical practice.