Study funded in part by the U.S. National Cancer Institute (NCI) finds presence of Epstein-Barr virus key to understanding how BL develops
In a collaborative effort involving more than 16 institutions around the globe, researchers from the Simon Fraser University (SFU)’s Department of Molecular Biology and Biochemistry have refined the classification of a rare cancer called Burkitt lymphoma (BL). They hope this will lead to more precise treatment options and, potentially, to improved survival rates for patients. The study was published in the journal Blood earlier this year.
BL most often develops in children or young adults and is fatal if untreated. Currently, the classification of BL depends on where the patient resides. The endemic variant of BL consistently occurs in regions where malaria is common, such as Africa and Papua-New Guinea, whereas the sporadic subtype develops in regions where malaria is not generally found.
SFU PhD candidate Bruno Grande and his team analyzed the genetic data of 106 BL tissue samples from paediatric patients in Africa, North America and Europe, sourced from the U.S. National Cancer Institute (NCI)’s Genomic Data Commons. Grande worked under the supervision of professor Ryan Morin at SFU. Daniela Gerhard, director of NCI’s Office of Cancer Genomics, is second author on the study and Louis Staudt, director of the NCI’s Center for Cancer Genomics is co-corresponding author. The team used a combination of whole-genome and transcriptome sequencing generated by the British Columbia Cancer Genome Sciences Centre under Director Marco Marra.
Using sophisticated computational methods to determine the molecular and genetic features of each patient sample, the team discovered that the presence of the Epstein-Barr virus (EBV) in the tumour is key to understanding BL, regardless of where the patient resides.
Grande says, “We have known about a relationship between BL and EBV for over 50 years, but we didn’t fully understand how this affected the development of BL.”
EBV is present in more than 90 per cent of cases in malaria-endemic regions, and in up to 30 per cent elsewhere.
“We examined tumour samples from all patients and found that EBV-positive tumours lacked important mutations in genes that play a role in apoptosis, also known as programmed cell death,” says Grande. “These data support a long-standing but unproven hypothesis that EBV disrupts apoptosis, and in turn, allows the tumour cells to grow into BL.”
BL is generally successfully treated with intensive chemotherapy available in resource-rich countries. One-year survival rates for American children often reach 90 per cent, which is double what is generally reached in some parts of Africa.
Grande was drawn to the research after learning of the disparity in patient outcomes.
“Most genomic research for BL has focused on the relatively curable and less common sporadic variant, despite the fact that most children who die from BL are endemic cases (i.e. cases from malaria-endemic regions such as equatorial Africa). This project was my way of trying to level the playing field in terms of research.”
The study was initiated by the Foundation for Burkitt Lymphoma Research based in Switzerland and funded in partnership with the National Cancer Institute (HHSN261200800001E) with salary support from the Terry Fox Research Institute.
Simon Fraser University