Publication Title
Clinical cancer research : an official journal of the American Association for Cancer Research
Document Type
Article
Publication Date
12-15-2018
Keywords
Animals; Antineoplastic Agents; Biomarkers, Tumor; Cell Line, Tumor; Chromosome Deletion; Chromosomes, Human, Pair 6; Disease Models, Animal; Gene Expression Regulation, Neoplastic; Glioma; Humans; Mice; Molecular Targeted Therapy; Oncogene Proteins, Fusion; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Proto-Oncogene Proteins; Real-Time Polymerase Chain Reaction; Xenograft Model Antitumor Assays
Abstract
PURPOSE: Gliomas, a genetically heterogeneous group of primary central nervous system tumors, continue to pose a significant clinical challenge. Discovery of chromosomal rearrangements involving kinase genes has enabled precision therapy, and improved outcomes in several malignancies.
EXPERIMENTAL DESIGN: Positing that similar benefit could be accomplished for patients with brain cancer, we evaluated The Cancer Genome Atlas (TCGA) glioblastoma dataset. Functional validation of the oncogenic potential and inhibitory sensitivity of discovered ROS1 fusions was performed using three independent cell-based model systems, and an
RESULTS:
CONCLUSIONS: Our findings highlight that CNS tumors should be specifically interrogated for these rare intrachromosomal 6q22 microdeletion events that generate actionable ROS1 fusions. ROS1 fusions in primary brain cancer may be amenable for clinical intervention with kinase inhibitors, and this holds the potential of novel treatment paradigms in these treatment-refractory cancer types, particularly in glioblastoma.
Area of Special Interest
Cancer
Specialty/Research Institute
Oncology
