Clinical and Pathological Characteristics of KEAP1- and NFE2L2-Mutated Non–Small Cell Lung Carcinoma (NSCLC)
| Autor: | Britta Kaminsky, Reinhard Büttner, Frank Ueckeroth, Anna Eisert, Jana Fassunke, Ulrich Gerigk, Carina Heydt, Yon-Dschun Ko, Mathieu Clément-Ziza, Lukas C. Heukamp, Thomas Geist, Jürgen Wolf, Matthias Scheffler, Katharina König, Anna Kron, Sabine Merkelbach-Bruse, Sebastian Michels, Monika Serke, Michaela Angelika Ihle, Rieke Frank, Michael Rauer, Rieke Fischer |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research Lung business.industry Histology In situ hybridization medicine.disease NFE2L2 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Carcinoma Cancer research Medicine Immunohistochemistry Adenocarcinoma business Pathological |
| Zdroj: | Clinical Cancer Research. 24:3087-3096 |
| ISSN: | 1557-3265 1078-0432 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|