Researchers discover fusion protein that promotes cancer via three distinct ways in pediatric brain tumors

CHOP's Adam Resnick

Scientists at The Children's Hospital of Philadelphia (CHOP) and the Dana Farber Cancer Institute have uncovered an important cancer-driving fusion protein that promotes a pediatric brain tumor via three distinct mechanisms.

Adam Resnick from CHOP along with Dana Farber scientists Keith Ligon and Rameen Beroukhim published their work in the journal Nature Genetics.

They investigated pediatric low-grade gliomas (PLGGs), a disease that represents the majority of child brain tumors. Despite PLGGs being a "low grade" tumor there may be serious consequences to the patient's future quality of life, which gives reason to search for causal mechanisms and treatment.

In a specific type of PLGGs that occur in the brain's temporal lobe (angiocentric gliomas), in virtually all tumor samples from 19 patients there was a common gene rearrangement of two genes: MYB and QKI.

The abnormal product of MYB-QKI leads to cancer survival in three ways. Firstly the protein produced from this gene fusion results in a smaller protein being formed, which is always active and can promote cancer. Secondly, an enhancer region which may control QKI gene expression moves nearer MYB as they fuse, giving rise to abnormal amounts of MYB-QKI protein, leading to a positive feedback loop and further driving cell proliferation. And lastly, the protective role of QKI as a tumor suppressor is dashed in the new MYB-QKI gene product.

The product of just two genes sticking together therefore results in a myriad of genomic and epigenomic interactions and explains the complexity of such an event in this tumor.

The identification of the MYB-QKI fusion gene in patients may enable doctors to more accurately diagnose the resulting PLGG and to direct treatment accordingly.

"Now that we better understand the three mechanisms involved, we may be better able to craft our treatment strategies against any of those mechanisms." Resnick said.

He continued: "the study expands our current understanding of cancer, by focusing attention on the multiple mechanisms occurring simultaneously, and bringing into relief how gene fusions may give rise to epigenomic dysregulation. Gene fusions occur in many other cancers in both children and adults, so our findings may apply more broadly to other cancers."

- here's the Nature Genetics article
- here's the release