Clinical and Pathological Characteristics of KEAP1- and NFE2L2-Mutated Non-Small Cell Lung Carcinoma (NSCLC)

Publication Date:
2018-07-03
Publisher:
The American Association for Cancer Research (AACR)
Print ISSN:
1078-0432
Electronic ISSN:
1557-3265
Topics:
Medicine
Published by:
http://www.aacr.org/
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autor Frank, R., Scheffler, M., Merkelbach-Bruse, S., Ihle, M. A., Kron, A., Rauer, M., Ueckeroth, F., König, K., Michels, S., Fischer, R., Eisert, A., Fassunke, J., Heydt, C., Serke, M., Ko, Y.-D., Gerigk, U., Geist, T., Kaminsky, B., Heukamp, L. C., Clement-Ziza, M., Büttner, R., Wolf, J.
beschreibung Purpose: KEAP1 and NFE2L2 mutations are associated with impaired prognosis in a variety of cancers and with squamous cell carcinoma formation in non–small cell lung cancer (NSCLC). However, little is known about frequency, histology dependence, molecular and clinical presentation as well as response to systemic treatment in NSCLC. Experimental Design: Tumor tissue of 1,391 patients with NSCLC was analyzed using next-generation sequencing (NGS). Clinical and pathologic characteristics, survival, and treatment outcome of patients with KEAP1 or NFE2L2 mutations were assessed. Results: KEAP1 mutations occurred with a frequency of 11.3% ( n = 157) and NFE2L2 mutations with a frequency of 3.5% ( n = 49) in NSCLC patients. In the vast majority of patients, both mutations did not occur simultaneously. KEAP1 mutations were found mainly in adenocarcinoma (AD; 72%), while NFE2L2 mutations were more common in squamous cell carcinoma (LSCC; 59%). KEAP1 mutations were spread over the whole protein, whereas NFE2L2 mutations were clustered in specific hotspot regions. In over 80% of the patients both mutations co-occurred with other cancer-related mutations, among them also targetable aberrations like activating EGFR mutations or MET amplification. Both patient groups showed different patterns of metastases, stage distribution and performance state. No patient with KEAP1 mutation had a response on systemic treatment in first-, second-, or third-line setting. Of NFE2L2 -mutated patients, none responded to second- or third-line therapy. Conclusions: KEAP1 - and NFE2L2 -mutated NSCLC patients represent a highly heterogeneous patient cohort. Both are associated with different histologies and usually are found together with other cancer-related, partly targetable, genetic aberrations. In addition, both markers seem to be predictive for chemotherapy resistance. Clin Cancer Res; 24(13); 3087–96. ©2018 AACR .
citation_standardnr 6297190
datenlieferant ipn_articles
feed_id 9363
feed_publisher The American Association for Cancer Research (AACR)
feed_publisher_url http://www.aacr.org/
insertion_date 2018-07-03
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/24/13/3087?rss=1
search_space articles
shingle_author_1 Frank, R., Scheffler, M., Merkelbach-Bruse, S., Ihle, M. A., Kron, A., Rauer, M., Ueckeroth, F., König, K., Michels, S., Fischer, R., Eisert, A., Fassunke, J., Heydt, C., Serke, M., Ko, Y.-D., Gerigk, U., Geist, T., Kaminsky, B., Heukamp, L. C., Clement-Ziza, M., Büttner, R., Wolf, J.
shingle_author_2 Frank, R., Scheffler, M., Merkelbach-Bruse, S., Ihle, M. A., Kron, A., Rauer, M., Ueckeroth, F., König, K., Michels, S., Fischer, R., Eisert, A., Fassunke, J., Heydt, C., Serke, M., Ko, Y.-D., Gerigk, U., Geist, T., Kaminsky, B., Heukamp, L. C., Clement-Ziza, M., Büttner, R., Wolf, J.
shingle_author_3 Frank, R., Scheffler, M., Merkelbach-Bruse, S., Ihle, M. A., Kron, A., Rauer, M., Ueckeroth, F., König, K., Michels, S., Fischer, R., Eisert, A., Fassunke, J., Heydt, C., Serke, M., Ko, Y.-D., Gerigk, U., Geist, T., Kaminsky, B., Heukamp, L. C., Clement-Ziza, M., Büttner, R., Wolf, J.
shingle_author_4 Frank, R., Scheffler, M., Merkelbach-Bruse, S., Ihle, M. A., Kron, A., Rauer, M., Ueckeroth, F., König, K., Michels, S., Fischer, R., Eisert, A., Fassunke, J., Heydt, C., Serke, M., Ko, Y.-D., Gerigk, U., Geist, T., Kaminsky, B., Heukamp, L. C., Clement-Ziza, M., Büttner, R., Wolf, J.
shingle_catch_all_1 Clinical and Pathological Characteristics of KEAP1- and NFE2L2-Mutated Non-Small Cell Lung Carcinoma (NSCLC)
Purpose: KEAP1 and NFE2L2 mutations are associated with impaired prognosis in a variety of cancers and with squamous cell carcinoma formation in non–small cell lung cancer (NSCLC). However, little is known about frequency, histology dependence, molecular and clinical presentation as well as response to systemic treatment in NSCLC. Experimental Design: Tumor tissue of 1,391 patients with NSCLC was analyzed using next-generation sequencing (NGS). Clinical and pathologic characteristics, survival, and treatment outcome of patients with KEAP1 or NFE2L2 mutations were assessed. Results: KEAP1 mutations occurred with a frequency of 11.3% ( n = 157) and NFE2L2 mutations with a frequency of 3.5% ( n = 49) in NSCLC patients. In the vast majority of patients, both mutations did not occur simultaneously. KEAP1 mutations were found mainly in adenocarcinoma (AD; 72%), while NFE2L2 mutations were more common in squamous cell carcinoma (LSCC; 59%). KEAP1 mutations were spread over the whole protein, whereas NFE2L2 mutations were clustered in specific hotspot regions. In over 80% of the patients both mutations co-occurred with other cancer-related mutations, among them also targetable aberrations like activating EGFR mutations or MET amplification. Both patient groups showed different patterns of metastases, stage distribution and performance state. No patient with KEAP1 mutation had a response on systemic treatment in first-, second-, or third-line setting. Of NFE2L2 -mutated patients, none responded to second- or third-line therapy. Conclusions: KEAP1 - and NFE2L2 -mutated NSCLC patients represent a highly heterogeneous patient cohort. Both are associated with different histologies and usually are found together with other cancer-related, partly targetable, genetic aberrations. In addition, both markers seem to be predictive for chemotherapy resistance. Clin Cancer Res; 24(13); 3087–96. ©2018 AACR .
Frank, R., Scheffler, M., Merkelbach-Bruse, S., Ihle, M. A., Kron, A., Rauer, M., Ueckeroth, F., König, K., Michels, S., Fischer, R., Eisert, A., Fassunke, J., Heydt, C., Serke, M., Ko, Y.-D., Gerigk, U., Geist, T., Kaminsky, B., Heukamp, L. C., Clement-Ziza, M., Büttner, R., Wolf, J.
The American Association for Cancer Research (AACR)
1078-0432
10780432
1557-3265
15573265
shingle_catch_all_2 Clinical and Pathological Characteristics of KEAP1- and NFE2L2-Mutated Non-Small Cell Lung Carcinoma (NSCLC)
Purpose: KEAP1 and NFE2L2 mutations are associated with impaired prognosis in a variety of cancers and with squamous cell carcinoma formation in non–small cell lung cancer (NSCLC). However, little is known about frequency, histology dependence, molecular and clinical presentation as well as response to systemic treatment in NSCLC. Experimental Design: Tumor tissue of 1,391 patients with NSCLC was analyzed using next-generation sequencing (NGS). Clinical and pathologic characteristics, survival, and treatment outcome of patients with KEAP1 or NFE2L2 mutations were assessed. Results: KEAP1 mutations occurred with a frequency of 11.3% ( n = 157) and NFE2L2 mutations with a frequency of 3.5% ( n = 49) in NSCLC patients. In the vast majority of patients, both mutations did not occur simultaneously. KEAP1 mutations were found mainly in adenocarcinoma (AD; 72%), while NFE2L2 mutations were more common in squamous cell carcinoma (LSCC; 59%). KEAP1 mutations were spread over the whole protein, whereas NFE2L2 mutations were clustered in specific hotspot regions. In over 80% of the patients both mutations co-occurred with other cancer-related mutations, among them also targetable aberrations like activating EGFR mutations or MET amplification. Both patient groups showed different patterns of metastases, stage distribution and performance state. No patient with KEAP1 mutation had a response on systemic treatment in first-, second-, or third-line setting. Of NFE2L2 -mutated patients, none responded to second- or third-line therapy. Conclusions: KEAP1 - and NFE2L2 -mutated NSCLC patients represent a highly heterogeneous patient cohort. Both are associated with different histologies and usually are found together with other cancer-related, partly targetable, genetic aberrations. In addition, both markers seem to be predictive for chemotherapy resistance. Clin Cancer Res; 24(13); 3087–96. ©2018 AACR .
Frank, R., Scheffler, M., Merkelbach-Bruse, S., Ihle, M. A., Kron, A., Rauer, M., Ueckeroth, F., König, K., Michels, S., Fischer, R., Eisert, A., Fassunke, J., Heydt, C., Serke, M., Ko, Y.-D., Gerigk, U., Geist, T., Kaminsky, B., Heukamp, L. C., Clement-Ziza, M., Büttner, R., Wolf, J.
The American Association for Cancer Research (AACR)
1078-0432
10780432
1557-3265
15573265
shingle_catch_all_3 Clinical and Pathological Characteristics of KEAP1- and NFE2L2-Mutated Non-Small Cell Lung Carcinoma (NSCLC)
Purpose: KEAP1 and NFE2L2 mutations are associated with impaired prognosis in a variety of cancers and with squamous cell carcinoma formation in non–small cell lung cancer (NSCLC). However, little is known about frequency, histology dependence, molecular and clinical presentation as well as response to systemic treatment in NSCLC. Experimental Design: Tumor tissue of 1,391 patients with NSCLC was analyzed using next-generation sequencing (NGS). Clinical and pathologic characteristics, survival, and treatment outcome of patients with KEAP1 or NFE2L2 mutations were assessed. Results: KEAP1 mutations occurred with a frequency of 11.3% ( n = 157) and NFE2L2 mutations with a frequency of 3.5% ( n = 49) in NSCLC patients. In the vast majority of patients, both mutations did not occur simultaneously. KEAP1 mutations were found mainly in adenocarcinoma (AD; 72%), while NFE2L2 mutations were more common in squamous cell carcinoma (LSCC; 59%). KEAP1 mutations were spread over the whole protein, whereas NFE2L2 mutations were clustered in specific hotspot regions. In over 80% of the patients both mutations co-occurred with other cancer-related mutations, among them also targetable aberrations like activating EGFR mutations or MET amplification. Both patient groups showed different patterns of metastases, stage distribution and performance state. No patient with KEAP1 mutation had a response on systemic treatment in first-, second-, or third-line setting. Of NFE2L2 -mutated patients, none responded to second- or third-line therapy. Conclusions: KEAP1 - and NFE2L2 -mutated NSCLC patients represent a highly heterogeneous patient cohort. Both are associated with different histologies and usually are found together with other cancer-related, partly targetable, genetic aberrations. In addition, both markers seem to be predictive for chemotherapy resistance. Clin Cancer Res; 24(13); 3087–96. ©2018 AACR .
Frank, R., Scheffler, M., Merkelbach-Bruse, S., Ihle, M. A., Kron, A., Rauer, M., Ueckeroth, F., König, K., Michels, S., Fischer, R., Eisert, A., Fassunke, J., Heydt, C., Serke, M., Ko, Y.-D., Gerigk, U., Geist, T., Kaminsky, B., Heukamp, L. C., Clement-Ziza, M., Büttner, R., Wolf, J.
The American Association for Cancer Research (AACR)
1078-0432
10780432
1557-3265
15573265
shingle_catch_all_4 Clinical and Pathological Characteristics of KEAP1- and NFE2L2-Mutated Non-Small Cell Lung Carcinoma (NSCLC)
Purpose: KEAP1 and NFE2L2 mutations are associated with impaired prognosis in a variety of cancers and with squamous cell carcinoma formation in non–small cell lung cancer (NSCLC). However, little is known about frequency, histology dependence, molecular and clinical presentation as well as response to systemic treatment in NSCLC. Experimental Design: Tumor tissue of 1,391 patients with NSCLC was analyzed using next-generation sequencing (NGS). Clinical and pathologic characteristics, survival, and treatment outcome of patients with KEAP1 or NFE2L2 mutations were assessed. Results: KEAP1 mutations occurred with a frequency of 11.3% ( n = 157) and NFE2L2 mutations with a frequency of 3.5% ( n = 49) in NSCLC patients. In the vast majority of patients, both mutations did not occur simultaneously. KEAP1 mutations were found mainly in adenocarcinoma (AD; 72%), while NFE2L2 mutations were more common in squamous cell carcinoma (LSCC; 59%). KEAP1 mutations were spread over the whole protein, whereas NFE2L2 mutations were clustered in specific hotspot regions. In over 80% of the patients both mutations co-occurred with other cancer-related mutations, among them also targetable aberrations like activating EGFR mutations or MET amplification. Both patient groups showed different patterns of metastases, stage distribution and performance state. No patient with KEAP1 mutation had a response on systemic treatment in first-, second-, or third-line setting. Of NFE2L2 -mutated patients, none responded to second- or third-line therapy. Conclusions: KEAP1 - and NFE2L2 -mutated NSCLC patients represent a highly heterogeneous patient cohort. Both are associated with different histologies and usually are found together with other cancer-related, partly targetable, genetic aberrations. In addition, both markers seem to be predictive for chemotherapy resistance. Clin Cancer Res; 24(13); 3087–96. ©2018 AACR .
Frank, R., Scheffler, M., Merkelbach-Bruse, S., Ihle, M. A., Kron, A., Rauer, M., Ueckeroth, F., König, K., Michels, S., Fischer, R., Eisert, A., Fassunke, J., Heydt, C., Serke, M., Ko, Y.-D., Gerigk, U., Geist, T., Kaminsky, B., Heukamp, L. C., Clement-Ziza, M., Büttner, R., Wolf, J.
The American Association for Cancer Research (AACR)
1078-0432
10780432
1557-3265
15573265
shingle_title_1 Clinical and Pathological Characteristics of KEAP1- and NFE2L2-Mutated Non-Small Cell Lung Carcinoma (NSCLC)
shingle_title_2 Clinical and Pathological Characteristics of KEAP1- and NFE2L2-Mutated Non-Small Cell Lung Carcinoma (NSCLC)
shingle_title_3 Clinical and Pathological Characteristics of KEAP1- and NFE2L2-Mutated Non-Small Cell Lung Carcinoma (NSCLC)
shingle_title_4 Clinical and Pathological Characteristics of KEAP1- and NFE2L2-Mutated Non-Small Cell Lung Carcinoma (NSCLC)
timestamp 2025-06-30T23:35:56.101Z
titel Clinical and Pathological Characteristics of KEAP1- and NFE2L2-Mutated Non-Small Cell Lung Carcinoma (NSCLC)
titel_suche Clinical and Pathological Characteristics of KEAP1- and NFE2L2-Mutated Non-Small Cell Lung Carcinoma (NSCLC)
topic WW-YZ
uid ipn_articles_6297190