Cell-Cycle and DNA-Damage Response Pathway Is Involved in Leptomeningeal Metastasis of Non-Small Cell Lung Cancer

被引：58

作者：

Fan, Yun ^{[1
]}

Zhu, Xuehua ^{[2
]}

Xu, Yan ^{[3
]}

Lu, Xuesong ^{[4
]}

Xu, Yanjun ^{[1
]}

Wang, Mengzhao ^{[3
]}

Xu, Haiyan ^{[4
]}

Ding, Jingyan ^{[2
]}

Ye, Xin ^{[2
]}

Fang, Luo ^{[5
]}

Huang, Zhiyu ^{[5
]}

Gong, Lei ^{[5
]}

Lu, Hongyang ^{[1
]}

Mao, Weimin ^{[1
]}

Hu, Min ^{[2
]}

机构：

[1] Zhejiang Canc Hosp, Key Lab Diag & Treatment Technol Thorac Oncol, Hangzhou, Zhejiang, Peoples R China

[2] AstraZeneca, IMED Asia, Shanghai, Peoples R China

[3] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Resp Med, Beijing, Peoples R China

[4] AstraZeneca, Res & Dev Informat, Shanghai, Peoples R China

[5] Zhejiang Canc Hosp, 1 Banshan East Rd, Hangzhou 310022, Zhejiang, Peoples R China

来源：

CLINICAL CANCER RESEARCH | 2018年 / 24卷 / 01期

关键词：

OLAPARIB MAINTENANCE THERAPY; SEROUS OVARIAN-CANCER; EGFR MUTATION STATUS; OPEN-LABEL; CEREBROSPINAL-FLUID; 1ST-LINE TREATMENT; BRAIN METASTASES; CHEMOTHERAPY; MULTICENTER; GEFITINIB;

D O I：

10.1158/1078-0432.CCR-17-1582

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Purpose: Leptomeningeal metastasis (LM) is a detrimental complication of non-small cell lung cancer (NSCLC) and associated with poor prognosis. However, the underlying mechanisms of the metastasis process are still poorly understood. Experimental Design: We performed next-generation panel sequencing of primary tumor tissue, cerebrospinal fluid (CSF), and matched normal controls from epidermal growth factor receptor (EGFR) mutation-positive NSCLC patients with LM. Results: The status of EGFR-activating mutations was highly concordant between primary tumor and CSF. PIK3CA aberrations were high in these patients, implicating an association with LM risk. Intriguingly, low overlapping of somatic protein-changing variants was observed between paired CSF and primary lesions, exhibiting tumor heterogeneity and genetic divergence. Moreover, genes with CSF-recurrent genomic alterations were predominantly involved in cell-cycle regulation and DNA-damage response (DDR), suggesting a role of the pathway in LM development. Conclusions: Our study has shed light on the genomic variations of NSCLC-LM, demonstrated genetic heterogeneity and divergence, uncovered involvement of cell-cycle and DDR pathway, and paved the way for potential therapeutic approaches to this unmet medical need. Clin Cancer Res; 24(1); 209-16. (C) 2017 AACR.

引用

页码：209 / 216

页数：8

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