May 10, 2019

An innovative way to look at genome rearrangements leads to new insights about ovarian cancer

Dr. Paul Krzyzanowski, Director of Genome Technology Translation at OICR.

Researchers look beyond an obvious hypothesis to connect patterns in gene expression with genome rearrangements, drawing attention to often-overlooked regions of the genome

If two different genes come together, the resulting gene fusion can have a new function that can cause or contribute to cancer. The discovery of cancer-causing gene fusions has led to the development of new therapies for many cancer types and sparked efforts to identify rearrangements that might yield new treatment targets. Often, however, researchers discover fusions with no effect on a cell, but a recent study has shown that the regions around these ‘fusions of unknown significance’ may be just as important to study as the fusion itself.

In their investigation into high grade serous ovarian cancer (HGSOC) – which has a five-year survival rate of only 20 per cent – the Genomics Program at OICR identified thousands of gene fusions and investigated the regions around these key points. As described in Scientific Reports, they found that the neighbouring regions are overexpressed – in essence, overactive – which may contribute to the cancerous nature of cells.

“Often, we find evidence of rearranged DNA without a clear picture of how rearrangements drive cancer,” says Dr. Paul Krzyzanowski, Director of Genome Technology Translation at OICR and primary author of the publication. “In this study, we found that the regions around gene fusions – in addition to the fusions themselves – are very active in cancer cells. This observation hints at the idea that we can look at broader genetic regions, and not just the location of a fusion by itself, to better understand how genomic rearrangements wreak havoc in cancer cells.”

In this study, we found that the regions around gene fusions – in addition to the fusions themselves – are very active in cancer cells

The observed overexpression of regions around fusions could be used to differentiate diseased cells from normal cells and lead to new cancer treatment approaches. The observations in this study are consistent with findings from the Pan-Cancer Analysis of Whole Genomes network, which identified patterns of overexpression in disturbed genomic regions across many cancer types.

Krzyzanowski says this work highlights a non-intuitive analytical approach for analyzing cancer-related gene fusions which will continue to be employed as OICR’s Ovarian Cancer Translational Research Initiative investigates how DNA rearrangements in ovarian cells drive cancer.

Read more about OICR’s Ovarian Cancer Translational Research Initiative or learn more about Genomics at OICR.