New technology revolutionizes cancer research
Martin Hirst, 604.707.5900 ext. 5471, mhirst@sfu.ca
Robert Holt, 604.675.8165, rholt@bcgsc.ca
Carol Thorbes, PAMR, 778.782.3035, cthorbes@sfu.ca
Research expertise at Simon Fraser University has helped scientists at the B.C. Cancer Agency’s (BCCA’s) Genome Sciences Centre (GSC) accomplish a world first, using the latest generation of genomic sequencing technology.
The sequencing equipment—faster and more economical to use than any of its predecessors—was recently used to map the entire genome of the pine beetle.
Now, SFU-led GSC research teams have used the equipment to map the genome of a metastatic breast cancer tumour, and have identified its mutations over a nine-year period.
To coincide with national breast cancer month, the researchers published their findings in the Oct. 8, 2009 issue of Nature.
The scientists compared the genomic profile of a primary tumour in an individual patient with that of subsequent metastatic tumour cells from the same patient.
The comparison revealed 32 gene mutations in the metastatic tumour, 19 of which were not found in the primary tumour. Until now, researchers didn’t know that these genes were related to breast cancer.
“This new and sophisticated sequencing technology established at the GSC by SFU researchers and our expertise in analyzing vast amounts of data enabled us to sequence the entire genomes of these tumour cells,” explains Rob Holt.
An SFU molecular biology and biochemistry (MBB) associate professor and GSC head of sequencing, Holt is one of five SFU scientists who oversaw the computational generation of data in this study.
Martin Hirst, an MBB adjunct professor who co-led this study’s data generation, says its findings pave the way for faster genomic profiling of all kinds of cancerous tumours.
“To date, only a handful of tumours have been sequenced and we are still at the very early stages of understanding the genetic heterogeneity of a given cancer type,” says Hirst, GSC group leader for technology development and functional genomics.
Other SFU scientists leading this study’s data generation are: Richard Moore, health sciences adjunct professor and BCA group leader for production sequencing, Marco Marra, GSC director; and Steven Jones, GSC head of bioinformatics. Marra and Jones are alumni turned adjunct and full professors, respectively, in MBB at SFU.
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Backgrounder: New technology revolutionizes cancer research
The complete genomic sequencing of a metastatic breast cancer tumour and its original cells lets scientists develop a much more detailed picture of cancer’s behaviour.
The sequencing technology and analysis used in this study are having the same impact on scientific understanding as the development of the magnifying glass and microscope did.
“Ultimately, genomic profiling combined with basic research into how gene products contribute to pathways which drive biological processes may lead to a revolution in cancer treatment,” says SFU MBB adjunct professor Martin Hirst. “Therapies could be tailored to an individual tumour. We’re talking about personalized medicine.”
In the Question and Answer session below, Hirst and SFU MBB associate professor Rob Holt tackle questions that couldn’t even be pondered before this technological development.
Q: If a patient’s cancer is actually multiple individual cancers with different personalities, how does that affect the likelihood of permanent remission, a cure or drugs with long term efficacy?
Hirst: I like to use the analogy of cancer as an infectious disease such as HIV. When cancer cells initially evolve they survive due to changes in their genetic makeup. That allows them to ignore signals that would tell a normal cell to stop proliferating and/or die.
When a selective pressure, such as targeted cancer therapy is applied, a subpopulation of mutated cells within the tumour survives the therapy and proliferates. These mutations may have existed within a subpopulation of cells within the primary tumour—maybe even in a single cell—or developed de novo during the course of treatment.
It may be that certain cancers can’t be cured outright, but, with repeated cycles of genomic profiling, managed as chronic diseases.
Holt: It has been known for some time that cancers are heterogeneous. The new genomic sequencing infrastructure we have now makes it possible to screen the full genomes of tumour cells and see, at the level of specific mutations, how the heterogeneity changes over time.”
Q: What does it tell us about cancer spread/metastasis if cancer cells aren’t uniform even in the early stages of a disease like breast cancer?
Holt: It is not yet known how to predict this. With enough data from enough patients it may be found in future that certain mutations are predictive.
A mutation may confer sensitivity to a known drug or, conversely, confer insensitivity. At this point this is all basic research. In principle, by understanding how all the mutations work an oncologist is better armed to make treatment decisions.
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Kelli
Wonderful, wonderful news to hear that this research is coming out of Canada -- and SFU no less!