Mutations in EMT-Related Genes in ALK Positive Crizotinib Resistant Non-Small Cell Lung Cancers
Abstract
:1. Introduction
2. Results
2.1. Patients
2.2. Whole Exome Sequencing
2.3. Variants Related to Crizotinib Treatment
2.4. Treatment-Related Copy Number Alterations
3. Discussion
4. Materials and Methods
4.1. Patient Inclusion
4.2. DNA Isolation
4.3. Whole Exome Sequencing
4.4. Immunohistochemistry
4.5. Data Analysis
4.6. WES-Based Analysis of CNAs
5. Conclusions
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Patient | Gender | Age at Diagnosis (Years) | PFS 1 (m) | Smoking Status (py 2) | Tumor Location | |
---|---|---|---|---|---|---|
Primary 4 | Resistant 5 | |||||
ALK4 | female | 34 | 15.9 | non-smoker | ovary | liver |
ALK6 | male | 55 | 9.5 | past-smoker (15) | cervical lymph node | glenoid |
ALK8 | male | 76 | 1.6 | past-smoker (NA 3) | lymph node mediastinal 4 right | not done |
ALK14 | female | 62 | 8.4 | current smoker (20) | brain occipital metastasis | mediastinal lymph node 7 |
ALK16 | female | 48 | 5.1 | past-smoker (18) | lung | lung |
Pathway Name | Patient(s) | Genes Mutated | Enrichment Score | Enrichment p-Value 1 |
---|---|---|---|---|
Proteoglycans in cancer 2 | ALK6 ALK14 | ANK2, FASLG, HSPG2, PTPN11, STAT3, VEGFA | 8.0 | 0.00 |
HIF-1 signaling pathway 2 | ALK6 ALK14 | ARNT, STAT3, VEGFA | 4.3 | 0.01 |
FoxO signaling pathway 2 | ALK6 ALK14 | FASLG, SMAD4, STAT3 | 3.7 | 0.03 |
ECM-receptor interaction 3 | ALK6 ALK14 | HSPG2, LAMA2 | 3.3 | 0.04 |
Adherens junction 3 | ALK6 ALK14 | CTNNA3, SMAD4 | 3.0 | 0.05 |
Ras signaling pathway | ALK14 | FASLG, PTPN11, VEGFA | 2.7 | 0.07 |
Jak-STAT signaling pathway | ALK6 ALK14 | PTPN11, STAT3 | 1.9 | ns |
PI3K-AKT signaling pathway | ALK14 | FASLG, LAMA2, VEGFA | 1.8 | ns |
Focal adhesion 3 | ALK14 | LAMA2, VEGFA | 1.6 | ns |
VEGF signaling pathway 3 | ALK14 | VEGFA | 1.3 | ns |
TGF-beta signaling pathway | ALK6 | SMAD4 | 1.2 | ns |
MAPK signaling pathway | ALK14 | FASLG, MAP3K20 | 1.1 | ns |
Wnt signaling pathway 3 | ALK6 | SMAD4 | 1.0 | ns |
Regulation of actin cytoskeleton | ALK6 | SCIN | 0.5 | ns |
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Wei, J.; Van der Wekken, A.J.; Saber, A.; Terpstra, M.M.; Schuuring, E.; Timens, W.; Hiltermann, T.J.N.; Groen, H.J.M.; Van den Berg, A.; Kok, K. Mutations in EMT-Related Genes in ALK Positive Crizotinib Resistant Non-Small Cell Lung Cancers. Cancers 2018, 10, 10. https://doi.org/10.3390/cancers10010010
Wei J, Van der Wekken AJ, Saber A, Terpstra MM, Schuuring E, Timens W, Hiltermann TJN, Groen HJM, Van den Berg A, Kok K. Mutations in EMT-Related Genes in ALK Positive Crizotinib Resistant Non-Small Cell Lung Cancers. Cancers. 2018; 10(1):10. https://doi.org/10.3390/cancers10010010
Chicago/Turabian StyleWei, Jiacong, Anthonie J. Van der Wekken, Ali Saber, Miente M. Terpstra, Ed Schuuring, Wim Timens, T. Jeroen N. Hiltermann, Harry J. M. Groen, Anke Van den Berg, and Klaas Kok. 2018. "Mutations in EMT-Related Genes in ALK Positive Crizotinib Resistant Non-Small Cell Lung Cancers" Cancers 10, no. 1: 10. https://doi.org/10.3390/cancers10010010