How genetic changes make some brain cancers more aggressive

WASHINGTON - A study has provided new insight into genetic changes that make some forms of glioblastoma, the most common type of primary brain cancer, more aggressive than others and have explained why they may not respond to certain therapies.

A multi-institutional team led by investigators from Memorial Sloan-Kettering Cancer Center led the study.

Glioblastoma has several subtypes, which are characterized by different genetic changes found in the tumor cells.

One common subtype is characterized by cells with increased signaling from a protein called platelet-derived growth factor receptor (PDGFR).

In the study, which involved screening patients’ tumor samples for PDGFR mutations, the researchers were surprised to find that almost half of all glioblastomas with excess copies of the PDGFR gene also had rearrangements in the gene itself, creating proteins that are continually turned on.

These rearrangements were either shortened forms of the protein or involved the fusion of the protein to another receptor.

Fusion genes have not been found in brain tumors previously but are well studied in certain types of leukemia, and more recently have been found in some solid tumors as well.

Much of the team’s work was made possible by data coming from The Cancer Genome Atlas (TCGA).

The presence of the rearrangements in the PDGFR gene suggest that these specific tumors have evolved to be dependent on signaling through this receptor, a target for several drugs under development.

The study has been published in the October 1 issue of the journal Genes ‘n’ Development. (ANI)