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Your search keyword '"Mirjam F. Mastik"' showing total 2 results
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2 results on '"Mirjam F. Mastik"'

1. Genomic Aberrations in Crizotinib Resistant Lung Adenocarcinoma Samples Identified by Transcriptome Sequencing.

Author

Ali Saber, Anthonie J van der Wekken, Klaas Kok, M Martijn Terpstra, Lisette J Bosman, Mirjam F Mastik, Wim Timens, Ed Schuuring, T Jeroen N Hiltermann, Harry J M Groen, and Anke van den Berg

Subjects
Medicine, Science
Abstract

ALK-break positive non-small cell lung cancer (NSCLC) patients initially respond to crizotinib, but resistance occurs inevitably. In this study we aimed to identify fusion genes in crizotinib resistant tumor samples. Re-biopsies of three patients were subjected to paired-end RNA sequencing to identify fusion genes using deFuse and EricScript. The IGV browser was used to determine presence of known resistance-associated mutations. Sanger sequencing was used to validate fusion genes and digital droplet PCR to validate mutations. ALK fusion genes were detected in all three patients with EML4 being the fusion partner. One patient had no additional fusion genes. Another patient had one additional fusion gene, but without a predicted open reading frame (ORF). The third patient had three additional fusion genes, of which two were derived from the same chromosomal region as the EML4-ALK. A predicted ORF was identified only in the CLIP4-VSNL1 fusion product. The fusion genes validated in the post-treatment sample were also present in the biopsy before crizotinib. ALK mutations (p.C1156Y and p.G1269A) detected in the re-biopsies of two patients, were not detected in pre-treatment biopsies. In conclusion, fusion genes identified in our study are unlikely to be involved in crizotinib resistance based on presence in pre-treatment biopsies. The detection of ALK mutations in post-treatment tumor samples of two patients underlines their role in crizotinib resistance.

Published
2016
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2. Genomic Aberrations in Crizotinib Resistant Lung Adenocarcinoma Samples Identified by Transcriptome Sequencing

Author

Anthonie J. van der Wekken, Mirjam F. Mastik, Ali Saber, Wim Timens, Harry J.M. Groen, Anke van den Berg, Ed Schuuring, Lisette J. Bosman, Martijn Terpstra, T. Jeroen N. Hiltermann, Klaas Kok, Groningen Research Institute for Asthma and COPD (GRIAC), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Targeted Gynaecologic Oncology (TARGON), Stem Cell Aging Leukemia and Lymphoma (SALL), Translational Immunology Groningen (TRIGR), and Guided Treatment in Optimal Selected Cancer Patients (GUTS)

Subjects
0301 basic medicine, Lung Neoplasms, Pyridines, Molecular biology, Gene Identification and Analysis, lcsh:Medicine, Cell Cycle Proteins, Artificial Gene Amplification and Extension, medicine.disease_cause, Polymerase Chain Reaction, Lung and Intrathoracic Tumors, Fusion gene, Transcriptome, 0302 clinical medicine, Sequencing techniques, Fusion Genes, Medicine and Health Sciences, Anaplastic lymphoma kinase, Anaplastic Lymphoma Kinase, DNA sequencing, lcsh:Science, Sanger sequencing, Mutation, Multidisciplinary, Serine Endopeptidases, RNA sequencing, Genomics, Middle Aged, CANCER, ALK INHIBITORS, ALIGNMENT, Oncology, 030220 oncology & carcinogenesis, Chromosomal region, symbols, Microtubule-Associated Proteins, medicine.drug, Research Article, Adult, Gene prediction, Biology, Adenocarcinoma, 03 medical and health sciences, symbols.namesake, Crizotinib, Gene Types, medicine, Genetics, Humans, Gene Prediction, Protein Kinase Inhibitors, Mutation Detection, lcsh:R, KINASE INHIBITORS, Dideoxy DNA sequencing, Membrane Proteins, Receptor Protein-Tyrosine Kinases, Biology and Life Sciences, Cancers and Neoplasms, Computational Biology, Reverse Transcriptase-Polymerase Chain Reaction, Genome Analysis, Non-Small Cell Lung Cancer, Research and analysis methods, 030104 developmental biology, Molecular biology techniques, Neurocalcin, RNA, Pyrazoles, lcsh:Q, Carrier Proteins
Abstract

ALK-break positive non-small cell lung cancer (NSCLC) patients initially respond to crizotinib, but resistance occurs inevitably. In this study we aimed to identify fusion genes in crizotinib resistant tumor samples. Re-biopsies of three patients were subjected to paired-end RNA sequencing to identify fusion genes using deFuse and EricScript. The IGV browser was used to determine presence of known resistance-associated mutations. Sanger sequencing was used to validate fusion genes and digital droplet PCR to validate mutations. ALK fusion genes were detected in all three patients with EML4 being the fusion partner. One patient had no additional fusion genes. Another patient had one additional fusion gene, but without a predicted open reading frame (ORF). The third patient had three additional fusion genes, of which two were derived from the same chromosomal region as the EML4-ALK. A predicted ORF was identified only in the CLIP4-VSNL1 fusion product. The fusion genes validated in the post-treatment sample were also present in the biopsy before crizotinib. ALK mutations (p.C1156Y and p.G1269A) detected in the re-biopsies of two patients, were not detected in pre-treatment biopsies. In conclusion, fusion genes identified in our study are unlikely to be involved in crizotinib resistance based on presence in pre-treatment biopsies. The detection of ALK mutations in post-treatment tumor samples of two patients underlines their role in crizotinib resistance.

Published
2015

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