February 5, 2020

Whole-genome analysis generates new insights into viruses involved in cancer

Dr. Ivan Borozan

OICR researchers scan more than 2,600 whole cancer genomes for traces of known and potentially unknown cancer-causing viruses, identifying new ways that these pathogens may eventually lead to the disease

It is estimated that viruses cause nearly 10 per cent of all cancers. These cancer-causing viruses – also known as oncoviruses – can make changes to normal cells that may eventually lead to the disease. As researchers better understand how oncoviruses cause cancer, they can develop new therapies and vaccines to prevent them from doing so.

In the most extensive exploration of cancer genomes to date, OICR researchers and collaborators discovered new insights into the mechanisms behind the seven known oncoviruses, and provided strong evidence that there are no other human cancer-causing viruses in existence.

Their study was published today in Nature Genetics, alongside more than 20 related publications from the Pan-Cancer Analysis of Whole Genomes Project, also known as the Pan-Cancer Project or PCAWG. The research group analyzed whole genome data from more than 2,600 patient tumours representing 35 different tumour types.

“The Pan-Cancer Project is one of the largest cancer genome projects to date,” says Dr. Ivan Borozan, Scientific Associate at OICR and leading co-author of the study. “This project allowed us to search for viruses in the most comprehensive collection of cancer genomes using the latest and most advanced techniques. To analyze this extensive dataset, we first had to develop computational tools and analysis pipelines that can efficiently process large-scale sequencing data and – at the same time – extract accurate information about minute amounts of the viral genome present in each individual sample. The results generated using these tools were then integrated to decipher molecular mechanisms that lead to the development of cancer.”

Our research points towards a future where these cancers can be treated more effectively, and potentially prevented in the first place.
– Dr. Ivan Borozan

The group discovered that an individual’s immune system, while trying to protect itself from a certain strain of the well-known human papillomavirus (HPV), may cause damage to normal DNA that lead to the development of bladder, head, neck and cervical cancers.

The study also found that the hepatitis B virus (HBV), which is linked to some liver cancers, causes damage in normal cells by integrating into human DNA close to TERT, a well-understood cancer-driving gene.

Spinoffs of this research initiative have led to important discoveries about the Epstein-Barr Virus (EBV) and how it can promote the development of stomach cancer.

“These findings can help us develop new vaccines or therapies that target these mechanisms,” says Borozan. “Our research points towards a future where these cancers can be treated more effectively, and potentially prevented in the first place.”

As new sequencing research initiatives emerge, the research group’s computational tools and pipelines – which are available for the research community to use – will help further explain the mechanisms behind this complex disease.


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