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. 2022 Dec 2:12:1014997.
doi: 10.3389/fonc.2022.1014997. eCollection 2022.

Distinct gene mutation profiles among multiple and single primary lung adenocarcinoma

Yadong Wang  1 , Guanghui Wang  1   2 , Haotian Zheng  1 , Jichang Liu  1 , Guoyuan Ma  2 , Gemu Huang  3 , Qingtao Song  3 , Jiajun Du  1   2
Affiliations

Distinct gene mutation profiles among multiple and single primary lung adenocarcinoma

Yadong Wang et al. Front Oncol. .

Abstract

With the development of technologies, multiple primary lung cancer (MPLC) has been detected more frequently. Although large-scale genomics studies have made significant progress, the aberrant gene mutation in MPLC is largely unclear. In this study, 141 and 44 lesions from single and multiple primary lung adenocarcinoma (SP- and MP-LUAD) were analyzed. DNA and RNA were extracted from formalin-fixed, paraffin-embedded tumor tissue and sequenced by using the next-generation sequencing-based YuanSu450TM gene panel. We systematically analyzed the clinical features and gene mutations of these lesions, and found that there were six genes differently mutated in MP-LUAD and SP-LUAD lesions, including RBM10, CDK4, ATRX, NTRK1, PREX2, SS18. Data from the cBioPortal database indicated that mutation of these genes was related to some clinical characteristics, such as TMB, tumor type, et al. Besides, heterogeneity analysis suggested that different lesions could be tracked back to monophyletic relationships. We compared the mutation landscape of MP-LUAD and SP-LUAD and identified six differentially mutated genes (RBM10, CDK4, ATRX, NTRK1, PREX2, SS18), and certain SNV loci in TP53 and EGFR which might play key roles in lineage decomposition in multifocal samples. These findings may provide insight into personalized prognosis prediction and new therapies for MP-LUAD patients.

Keywords: lung adenocarcinoma; multifocal lung cancer; multiple primary lung cancer; mutation; next generation sequencing.

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Conflict of interest statement

Authors GH and QS are employed by Amoy Diagnostics Co., LTD. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Correlation analysis of smoking amount with the largest lesion diameter of SP-(A) and MP-LUAD (B).
Figure 2
Figure 2
Comparation of SP- and MP-LUAD lesions. (A)The waterfall plot of tumor somatic mutation established based on the SP-LUAD (left) and MP-LUAD (right) cohort. (B, C, E) The difference of mutation frequency of common mutated genes between SP- and MP-LUAD lesions. (D) Six genes statistically different mutated among these two cohorts, including RBM10, CDK4, ATRX, NTRK1, PREX2, SS18. (F, G) Mutation Frequency of SP- and MP-LUAD lesions. * p<0.05.
Figure 3
Figure 3
(A, B) Mutation types of SP-(A) and MP-LUAD (B) lesions. (C, D) Co-mutation analysis of SP-(C) and MP-LUAD (D) lesions. (E) The common co-mutated genes among SP- and MP-LUAD lesions. * p<0.05.
Figure 4
Figure 4
Characteristics of the six differently mutated genes. (A) Gene alterations obtained from cBioPortal database. (B) Gene location on chromosomes. (C) Gene CNV analysis using TCGA data. (D) Clinical correlation analysis of six genes using cBioPortal database. * p<0.05, *** p<0.001.
Figure 5
Figure 5
Differential expressed gene based on the mutation status of the six genes. (A) Volcano figure of differently expressed genes from cBioPortal database. (B–D) GO (B) and KEGG (C, D) analysis based on the differently expressed genes.
Figure 6
Figure 6
Gene alterations and polygenetic tree of the triple-primary LUAD lesions.
Figure 7
Figure 7
Gene alterations and polygenetic tree of the dual-primary LUAD lesions.
See this image and copyright information in PMC

References

    1. Huang C, Qu X, Du J. Proportion of lung adenocarcinoma in female never-smokers has increased dramatically over the past 28 years. J Thorac Dis (2019) 11(7):2685–8. doi: 10.21037/jtd.2019.07.08 - DOI - PMC - PubMed
    1. Li M, Wan Y, Zhang L, Zhou L-N, Shi Z, Zhang R, et al. . Synchronous multiple lung cancers presenting as multifocal pure ground glass nodules: are whole-body positron emission tomography/computed tomography and brain enhanced magnetic resonance imaging necessary? Transl Lung Cancer Res (2019) 8(5):649–57. doi: 10.21037/tlcr.2019.09.10 - DOI - PMC - PubMed
    1. Tie H, Luo J, Shi R, Li Z, Chen D, Wu Q. Characteristics and prognosis of synchronous multiple primary lung cancer after surgical treatment: A systematic review and meta-analysis of current evidence. Cancer Med (2021) 10(2):507–20. doi: 10.1002/cam4.3614 - DOI - PMC - PubMed
    1. Zhou LN, Wu N, Zhao SJ, Yang L, Wang YL, Wang RB, et al. . [HRCT features differentiate synchronous multiple primary lung adenocarcinomas from intrapulmonary metastases]. Zhonghua Zhong Liu Za Zhi (2020) 42(6):449–55. doi: 10.3760/cma.j.cn112152-20200227-00126 - DOI - PubMed
    1. Chen K, Chen W, Cai J, Yang F, Lou F, Wang X, et al. . Favorable prognosis and high discrepancy of genetic features in surgical patients with multiple primary lung cancers. J Thorac Cardiovasc Surg (2018) 155(1):371–379. doi: 10.1016/j.jtcvs.2017.08.141 - DOI - PubMed