Cell-Cycle and DNA-Damage Response Pathway Is Involved in Leptomeningeal Metastasis of Non-Small Cell Lung Cancer
Fan, Y., Zhu, X., Xu, Y., Lu, X., Xu, Y., Wang, M., Xu, H., Ding, J., Ye, X., Fang, L., Huang, Z., Gong, L., Lu, H., Mao, W., Hu, M.
The American Association for Cancer Research (AACR)
Published 2018
The American Association for Cancer Research (AACR)
Published 2018
| Publication Date: |
2018-01-04
|
|---|---|
| Publisher: |
The American Association for Cancer Research (AACR)
|
| Print ISSN: |
1078-0432
|
| Electronic ISSN: |
1557-3265
|
| Topics: |
Medicine
|
| Published by: |
| _version_ | 1836398730028253184 |
|---|---|
| autor | Fan, Y., Zhu, X., Xu, Y., Lu, X., Xu, Y., Wang, M., Xu, H., Ding, J., Ye, X., Fang, L., Huang, Z., Gong, L., Lu, H., Mao, W., Hu, M. |
| beschreibung | 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. ©2017 AACR . |
| citation_standardnr | 6128588 |
| datenlieferant | ipn_articles |
| feed_id | 9363 |
| feed_publisher | The American Association for Cancer Research (AACR) |
| feed_publisher_url | http://www.aacr.org/ |
| insertion_date | 2018-01-04 |
| journaleissn | 1557-3265 |
| journalissn | 1078-0432 |
| publikationsjahr_anzeige | 2018 |
| publikationsjahr_facette | 2018 |
| publikationsjahr_intervall | 7984:2015-2019 |
| publikationsjahr_sort | 2018 |
| publisher | The American Association for Cancer Research (AACR) |
| quelle | Clinical Cancer Research |
| relation | http://clincancerres.aacrjournals.org/cgi/content/short/24/1/209?rss=1 |
| search_space | articles |
| shingle_author_1 | Fan, Y., Zhu, X., Xu, Y., Lu, X., Xu, Y., Wang, M., Xu, H., Ding, J., Ye, X., Fang, L., Huang, Z., Gong, L., Lu, H., Mao, W., Hu, M. |
| shingle_author_2 | Fan, Y., Zhu, X., Xu, Y., Lu, X., Xu, Y., Wang, M., Xu, H., Ding, J., Ye, X., Fang, L., Huang, Z., Gong, L., Lu, H., Mao, W., Hu, M. |
| shingle_author_3 | Fan, Y., Zhu, X., Xu, Y., Lu, X., Xu, Y., Wang, M., Xu, H., Ding, J., Ye, X., Fang, L., Huang, Z., Gong, L., Lu, H., Mao, W., Hu, M. |
| shingle_author_4 | Fan, Y., Zhu, X., Xu, Y., Lu, X., Xu, Y., Wang, M., Xu, H., Ding, J., Ye, X., Fang, L., Huang, Z., Gong, L., Lu, H., Mao, W., Hu, M. |
| shingle_catch_all_1 | Cell-Cycle and DNA-Damage Response Pathway Is Involved in Leptomeningeal Metastasis of Non-Small Cell Lung Cancer 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. ©2017 AACR . Fan, Y., Zhu, X., Xu, Y., Lu, X., Xu, Y., Wang, M., Xu, H., Ding, J., Ye, X., Fang, L., Huang, Z., Gong, L., Lu, H., Mao, W., Hu, M. The American Association for Cancer Research (AACR) 1078-0432 10780432 1557-3265 15573265 |
| shingle_catch_all_2 | Cell-Cycle and DNA-Damage Response Pathway Is Involved in Leptomeningeal Metastasis of Non-Small Cell Lung Cancer 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. ©2017 AACR . Fan, Y., Zhu, X., Xu, Y., Lu, X., Xu, Y., Wang, M., Xu, H., Ding, J., Ye, X., Fang, L., Huang, Z., Gong, L., Lu, H., Mao, W., Hu, M. The American Association for Cancer Research (AACR) 1078-0432 10780432 1557-3265 15573265 |
| shingle_catch_all_3 | Cell-Cycle and DNA-Damage Response Pathway Is Involved in Leptomeningeal Metastasis of Non-Small Cell Lung Cancer 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. ©2017 AACR . Fan, Y., Zhu, X., Xu, Y., Lu, X., Xu, Y., Wang, M., Xu, H., Ding, J., Ye, X., Fang, L., Huang, Z., Gong, L., Lu, H., Mao, W., Hu, M. The American Association for Cancer Research (AACR) 1078-0432 10780432 1557-3265 15573265 |
| shingle_catch_all_4 | Cell-Cycle and DNA-Damage Response Pathway Is Involved in Leptomeningeal Metastasis of Non-Small Cell Lung Cancer 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. ©2017 AACR . Fan, Y., Zhu, X., Xu, Y., Lu, X., Xu, Y., Wang, M., Xu, H., Ding, J., Ye, X., Fang, L., Huang, Z., Gong, L., Lu, H., Mao, W., Hu, M. The American Association for Cancer Research (AACR) 1078-0432 10780432 1557-3265 15573265 |
| shingle_title_1 | Cell-Cycle and DNA-Damage Response Pathway Is Involved in Leptomeningeal Metastasis of Non-Small Cell Lung Cancer |
| shingle_title_2 | Cell-Cycle and DNA-Damage Response Pathway Is Involved in Leptomeningeal Metastasis of Non-Small Cell Lung Cancer |
| shingle_title_3 | Cell-Cycle and DNA-Damage Response Pathway Is Involved in Leptomeningeal Metastasis of Non-Small Cell Lung Cancer |
| shingle_title_4 | Cell-Cycle and DNA-Damage Response Pathway Is Involved in Leptomeningeal Metastasis of Non-Small Cell Lung Cancer |
| timestamp | 2025-06-30T23:31:43.491Z |
| titel | Cell-Cycle and DNA-Damage Response Pathway Is Involved in Leptomeningeal Metastasis of Non-Small Cell Lung Cancer |
| titel_suche | Cell-Cycle and DNA-Damage Response Pathway Is Involved in Leptomeningeal Metastasis of Non-Small Cell Lung Cancer |
| topic | WW-YZ |
| uid | ipn_articles_6128588 |