The CGGA research group has identified a new fusion protein found in approximately 15 percent of secondary glioblastomas. The finding offers new insights into the cause of this cancer and provides a therapeutic target for personalized oncologic care. The findings were published on Genome Research(Genome Res. 2014 Nov;24(11):1765-73. doi: 10.1101/gr.165126.113) and was notified as "Noteworthy" paper.
In this study, we used a technology called RNA-Seq to study the RNA sequences derived from 272 clinical tumor specimens from patients afflicted with secondary glioblastoma or precursor forms of this tumor.
The study revealed that the RNA sequences of brain cancers become progressively more abnormal as the tumor become more malignant. Specifically, the frequency of aberrant RNAs fusing gene sequences not normally found next to one another increased with tumor grade. Most of these fusion junctions occur in seemingly random locations. However, transcripts involving fusions of the PTPRZ and MET gene were found repeatedly in clinical specimens derived from different patients. The study estimates that 15 percent of the secondary glioblastoma harbor this fusion.
The recurrent nature of this fusion transcript suggests that the fusion did not arise by chance. Instead, it’s likely that the fusion actively contributes to the biologic behavior of the tumor. Supporting this hypothesis, we demonstrated that glioblastoma cells expressing the PTPRZ-MET fusion are more invasive and patients afflicted with these tumors showed particularly poor survival relative to other secondary glioblastoma patients.
One of the most important implications of the work is that inhibitors against the MET oncoprotein are available for clinical use. Secondary glioblastomas harboring the PTPRZ-MET fusion may be exquisitely sensitive to these inhibitors. Matching MET inhibitors to genotype of the glioblastoma affords us a unique opportunity to personalize oncologic care.
(Adapted from UC San Diego News Center)