Academic Journal
Concomitant mutation status of ALK-rearranged non-small cell lung cancers and its prognostic impact on patients treated with crizotinib
| العنوان: | Concomitant mutation status of ALK-rearranged non-small cell lung cancers and its prognostic impact on patients treated with crizotinib |
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| المؤلفون: | Li, Jingjing, Zhang, Bin, Zhang, Yu, Xu, Feng, Zhang, Zhenfa, Shao, Lin, Yan, Chunhe, Ulivi, Paola, Denis, Marc G., Christopoulos, Petros, de Montpreville, Vincent Thomas, Bernicker, Eric H., van der Wekken, Anthonie J., Wang, Changli, Yue, Dongsheng |
| المصدر: | Li , J , Zhang , B , Zhang , Y , Xu , F , Zhang , Z , Shao , L , Yan , C , Ulivi , P , Denis , M G , Christopoulos , P , de Montpreville , V T , Bernicker , E H , van der Wekken , A J , Wang , C & Yue , D 2021 , ' Concomitant mutation status of ALK-rearranged non-small cell lung cancers and its prognostic impact on patients treated with crizotinib ' , Translational lung cancer research , vol. 10 , no. 3 .... |
| سنة النشر: | 2021 |
| المجموعة: | University of Groningen research database |
| مصطلحات موضوعية: | Anaplastic lymphoma kinase rearrangement (ALK rearrangement), ALK fusion, concomitant mutation, next-generation sequencing (NGS), non-small cell lung cancer (NSCLC), crizotinib, ANAPLASTIC LYMPHOMA KINASE, SURVIVAL, GENE, DISCOVERY, VARIANTS, EFFICACY, PREDICT, GENOME, FISH, EGFR |
| الوصف: | Background: In non-small cell lung cancer (NSCLC), anaplastic lymphoma kinase (ALK) rearrangement characterizes a subgroup of patients who show sensitivity to ALK tyrosine kinase inhibitors (TKIs). However, the prognoses of these patients are heterogeneous. A better understanding of the genomic alterations occurring in these tumors could explain the prognostic heterogeneity observed in these patients. Methods: We retrospectively analyzed 96 patients with NSCLC with ALK detected by immunohistochemical staining (VENTANA anti-ALK(D5F3) Rabbit Monoclonal Primary Antibody). Cancer tissues were subjected to next-generation sequencing using a panel of 520 cancer-related genes. The genomic landscape, distribution of ALK fusion variants, and clinicopathological characteristics of the patients were evaluated. The correlations of genomic alterations with clinical outcomes were also assessed. Results: Among the 96 patients with immunohistochemically identified ALK fusions, 80 (83%) were confirmed by next-generation sequencing. TP53 mutation was the most commonly co-occurring mutation with ALK rearrangement. Concomitant driver mutations [2 Kirsten rat sarcoma viral oncogene homolog (KRAS) G12, 1 epidermal growth factor receptor (EGFR) 19del, and 1 MET exon 14 skipping] were also observed in 4 adenocarcinomas. Echinoderm microtubule associated protein-like 4 (EML4)-ALK fusions were identified in 95% of ALK-rearranged patients, with 16.2% of them also harboring additional non-EML4- ALK fusions. Nineteen non-EML4 translocation partners were also discovered, including 10 novel ones. Survival analyses revealed that patients concurrently harboring PIK3R2 alterations showed a trend toward shorter progression-free survival (6 vs. 13 months, P=0.064) and significantly shorter overall survival (11 vs. 32 months, P=0.004) than did PIK3R2-wild-type patients. Patients with concomitant alterations in PI3K the signaling pathway also had a shorter median overall survival than those without such alterations (23 vs. 32 months, P=0.014), ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| DOI: | 10.21037/tlcr-21-160 |
| الاتاحة: | https://hdl.handle.net/11370/98f84ba1-2878-476e-b01e-027e92920d98 https://research.rug.nl/en/publications/98f84ba1-2878-476e-b01e-027e92920d98 https://doi.org/10.21037/tlcr-21-160 https://pure.rug.nl/ws/files/177460331/50479_PB10_8429_R3.pdf |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.9585938F |
| قاعدة البيانات: | BASE |
| DOI: | 10.21037/tlcr-21-160 |
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