Research conducted at the UCSD School of Medicine has led to the identification of a new fusion protein, PTPRZ-MET, found in 15 percent of secondary glioblastomas, or GBMs. The findings, published earlier this month in the online edition of Genome Research, offer valuable insight into the aggressiveness of the GBM brain tumors.

Dr. Clark Chen, vice chairman of Neurosurgery Research and Academic Development and Dr. Bob Carter.,. professor of surgery and chief of neurosurgery, were among the principal investigators. Both Chen and Carter are researchers at the Moores Cancer Center.

In their study, Chen and Carter used a technology called RNA-Seq, a method typically used to identify and quantify both rare and common transcripts, to identify several new protein combinations. They collected data from 272 clinical tumor specimens taken from patients diagnosed with either secondary glioblastoma or a form of the cancer’s precursor.

While past genomic profiling has yielded understanding of primary glioblastoma, secondary glioblastoma has remained a relative mystery. In most cases, primary glioblastoma appears in older subjects with little to no history of malignant precursors. Secondary glioblastoma, the more deadly of the two, more often appears in younger patients and progresses from low-grade, less aggressive tumors into full-blown GBMs.

The study was meant to profile the changing RNA landscape of GBMs during the progression of the tumor.

It discovered a recurrent fusion of the PTPRZ and MET genes in the transcripts of those affected by secondary glioblastoma. Such genes are not normally found next to each other, and most of the fusion junctions identified occurred in seemingly random locations. These findings revealed that the RNA sequences of brain tumors grow increasingly more abnormal as they become more malignant. The PTPRZ-MET fusion proved to be extremely aggressive, and patients afflicted with such a fusion showed significantly higher mortality rates relative to patients afflicted with non PTPRZ-MET-harboring GBMs.

The further implications of this study could mean that research has taken another step towards a more personalized oncological care.

Still, Dr. Jie Li, co-author of the paper, emphasizes that personal care could still be a ways into the future.

“These patients may have or may not have this PTPRZ-MET protein,” Li said. “We hope we can see some kind of affect by the inhibitor to suppress the tumor growth and prolong survival.”

Researchers are unsure if, over time, other pathways will become activated in order to replace the inhibited pathway within the tumor cell.