May 10, 2019
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.
December 13, 2018
What can we gain from looking at the outliers?: An investigation into long and short-term ovarian cancer survivors
Researchers investigate the clinical, molecular and microenvironment factors that contribute to extreme therapy response and resistance in ovarian cancer patients
Some patients with high-grade serous ovarian cancer (HGSOC) respond exceptionally well to therapy, while others experience rapid disease relapse. The mechanisms behind these disparate outcomes are poorly understood, but a group of researchers based at the Princess Margaret Cancer Centre (PM) supported by OICR’s Ovarian Cancer Translational Research Initiative (TRI) are working to change that.Continue reading – What can we gain from looking at the outliers?: An investigation into long and short-term ovarian cancer survivors
November 6, 2018
Researchers studying ovarian cancer identify adapter protein 3BP2 as a key component of immune system function and a powerful tool that could be used to activate the immune system against hidden tumour cells.
August 9, 2017
A newly published paper in Genetics in Medicine has reinforced the fundamental importance of collecting information about genetic variances in a single large database. With so much important genetic information being used globally to understand the underlying genetic influences of diseases, researchers and clinicians need an accessible repository to share this information.
July 12, 2017
Given the advancements in treating many other types of cancer, it may come as a surprise that outcomes for patients with the most deadly form of ovarian cancer have not improved in 50 years. This form, known as High Grade Serous Ovarian Cancer (HGSOC), accounts for 80 per cent of ovarian cancer deaths in Canada. Surgery and chemotherapy can be effective, but ultimately three-quarters of women with HGSOC will see their disease return. To deliver better outcomes for patients, OICR has launched a new ‘all star team’ of ovarian cancer researchers.
May 25, 2017
OICR launches five all-star teams of Ontario scientists to tackle some of the deadliest forms of cancer
Great strides have been made in cancer research, but much work remains to develop better treatments for the most lethal cancers and to advance new anti-cancer technologies. OICR is taking on a new approach, building on the success of the Institute’s first ten years and Ontario’s strength in particular cancer research areas. Reza Moridi, Ontario’s Minister of Research, Innovation and Science announced that the Institute is funding five collaborative, cross-disciplinary and inter-institutional Translational Research Initiatives (TRIs) with a total of $24 million over the next two years.
The TRIs will bring together some of the top cancer researchers in Ontario and be led by internationally renowned Ontario scientists. Each team will focus on a certain type of cancer or therapeutic technology. To maximize the positive impact of research on patients, the TRIs all incorporate clinical trials into their design. The TRIs, which were selected by an International Scientific Review Panel, are:
- Acute Leukemia TRI (led by Drs. John Dick and Aaron Schimmer at the University Health Network (UHN))
- Brain Cancer TRI (led by Drs. Peter Dirks and Michael Taylor at SickKids)
- Immuno-oncology TRI (ACTION) (led by Drs. John Bell and Marcus Butler at The Ottawa Hospital and UHN)
- Ovarian Cancer TRI (led by Drs. Amit Oza and Rob Rottapel at UHN)
- Pancreatic Cancer TRI (PanCuRx) (led by Dr. Steven Gallinger at UHN)
The funding will also support Early Prostate Cancer Developmental Projects led by Drs. Paul Boutros and George Rodriguez.
“In just over 10 years, the Ontario Institute for Cancer Research has become a global centre of excellence that is moving the province to the forefront of discovery and innovation in cancer research. It is home to outstanding Ontario scientists, who are working together to ease the burden of cancer in our province and around the world,” said Moridi.
“Collaboration and translational research are key to seeing that the innovative technologies being developed in Ontario reach the clinic and help patients,” said Mr. Peter Goodhand, President of OICR. “These TRIs represent a unique and significant opportunity to impact clinical cancer care in the province.”
— SickKids_TheHospital (@SickKidsNews) May 25, 2017
— UHN (@UHN_News) May 25, 2017
— The Ottawa Hospital (@OttawaHospital) May 25, 2017
May 25, 2017
OICR launches five large-scale Ontario research initiatives to combat some of the most deadly cancers
Toronto (May 25, 2017) – Reza Moridi, Ontario’s Minister of Research, Innovation and Science, today announced the Ontario Institute for Cancer Research is launching five unique, cross-disciplinary, multi-institutional Translational Research Initiatives (TRIs), each focused on a single type of or treatment approach to cancer. With $24 million in funding over two years, the TRIs will bring together world-leading scientists to tackle some of the most difficult to treat cancers and test innovative solutions to some of the most serious challenges in cancer today.
The TRIs build on Ontario’s proven strengths in areas such as stem cells, immuno-oncology, pediatric cancers, genomics, clinical trials and informatics. Working together, the province’s top scientists and clinicians will accelerate the development of much needed solutions for patients around the globe, with a focus on acute leukemia and brain, ovarian and pancreatic cancers. Each TRI includes clinical trials to maximize patient impact.