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23.01.2019 | Original Article – Clinical Oncology

Comparative analysis of co-occurring mutations of specific tumor suppressor genes in lung adenocarcinoma between Asian and Caucasian populations

verfasst von: Yiliang Zhang, Yuan Ma, Yuan Li, Xuxia Shen, Yongfu Yu, Yunjian Pan, Yang Zhang, Difan Zheng, Yue Zhao, Ting Ye, Bin Li, Hong Hu, Yihua Sun, Yawei Zhang, Jiaqing Xiang, Haiquan Chen

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 3/2019

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Abstract

Introduction

Mutated tumor suppressor genes (TSG) such as TP53, STK11, and MGA are widely-reported. We hypothesized the presence of single mutation or co-occurring mutations in these specific genes may represent a significant therapeutic target for lung adenocarcinoma.

Methods

We sequenced lung adenocarcinoma samples from 677 East-Asian patients, combined them with those from cBioPortal public database (including TCGA) and performed a comparative analysis between Asian and Caucasian populations.

Results

East-Asian lung adenocarcinomas presented distinct driver-mutational distribution compared to that of Caucasians (79% vs 56%, p < 0.001). Similar results were observed in TSG mutations of TP53 (35% vs 46%, p = 0.150), STK11 (4% vs 17%, p = 0.006) and MGA (10% vs 4%, p = 0.166). Compared with none-mutational cases, the patients harboring TSG mutations are more likely to be male (p = 0.009), smokers (p < 0.001), and more advanced disease (p = 0.004). In addition, the TSG-mutated tumors had poorer differentiation (p < 0.001), and more likely to be solid or micropapillary-predominant adenocarcinomas (p < 0.001). Survival analysis showed that both overall survival (OS, p < 0.001) and post-recurrence survival (PRS, p < 0.001) became worse with the accumulation of TSG mutations. However, the prognostic variety was not found in Caucasian patients. Moreover, multivariate analysis proved the accumulation of TSG mutations independently predicts both unfavorable OS (HR = 0.435, 95% CI 0.245–0.774, p = 0.005) and PRS (HR = 0.491, 95% CI 0.269–0.894, p = 0.020) in East-Asian patients, adjusting all other survival-associated factors.

Conclusions

Co-occurring mutations of specific TSGs define unfavorable subgroups of lung adenocarcinoma, implying that the tumor promotion mechanisms contribute to the heterogeneity in tumor evolution. However, the Caucasian population did not show the same results, providing insights into the molecular basis underlying the striking racial disparities of this disease and evidence for different gene-panel designs for different population in the purpose of targeted therapy.
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Metadaten
Titel
Comparative analysis of co-occurring mutations of specific tumor suppressor genes in lung adenocarcinoma between Asian and Caucasian populations
verfasst von
Yiliang Zhang
Yuan Ma
Yuan Li
Xuxia Shen
Yongfu Yu
Yunjian Pan
Yang Zhang
Difan Zheng
Yue Zhao
Ting Ye
Bin Li
Hong Hu
Yihua Sun
Yawei Zhang
Jiaqing Xiang
Haiquan Chen
Publikationsdatum
23.01.2019
Verlag
Springer Berlin Heidelberg
Erschienen in
Journal of Cancer Research and Clinical Oncology / Ausgabe 3/2019
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-018-02828-5

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