The possibility of using a patient's genetic information to create personalized therapies to battle cancer is one step closer to reality after Canadian scientists decoded, for the first time, the entire genome of a patient's metastatic breast cancer.
It's a landmark achievement that sheds light on how cancer develops and provides new insights into how to fight it.
"I'm excited by the possibilities," said Samuel Aparicio, the head of the department of breast and molecular oncology at the B.C. Cancer Agency and one of the lead scientists involved with the discovery. "In fact, I never thought I would see in my professional lifetime that it would become possible to routinely sequence genomes in the way that we're now doing."
Genomes contain all of the biological information of a living organism, and that information is housed in DNA. There are about three billion "letters" or building blocks in the human genome. When cells divide, all three billion building blocks must be copied. But mistakes in the copying process can sometimes occur, and those mutations can, in some cases, cause cells to grow in an uncontrolled way - which is how cancer develops.
In decoding the metastatic breast-cancer genome, which contains all of the genetic information of a patient's cancer, scientists were able to identify all of the mutations in the tumour, a feat that has never before been accomplished.
But the breakthrough didn't stop there. Once all of the tumour mutations of the developed cancer were identified - a total of 32 were found - scientists had the information to look back and see which of those mutations were present in the patient's original, primary tumour.
They discovered that only 11 of the 32 mutations were present in the original tumour, with only five of those present in all of the original cancer cells, meaning that even in the early stages, cancer cells aren't uniform. That's significant because it proves even from the outset, cancer cells contain different mutations which change over time.
While scientists have theorized that cancer cells can differ, even in a single individual, until now it has never been possible to sequence the cancer genome and determine what mutations are present and how they evolve.
"I think we're getting used to the idea an individual patient's cancer is itself multiple individual cancers that may behave differently," said Dr. Aparicio, who holds the Canada research chair in molecular oncology and is the Nan and Lorraine Robertson chair of breast-cancer research at the University of British Columbia.
The findings, discovered by a research team led by Dr. Aparicio and Marco Marra, director of the Michael Smith Genome Sciences Centre at the B.C. Cancer Agency, are published today in the journal Nature.
A major portion of the money used to fund the research came from the B.C. Cancer Foundation's Weekend to End Breast Cancer walk, as well as donations raised across the province during the annual breast-cancer walk over the past six years. Funding also came from other groups, including the Canadian Breast Cancer Foundation.
The next major challenge will be interpreting the mutations to understand their significance and determine which mutations are vulnerable to which treatments.
Eventually, scientists hope to decode cancer genomes from a large number of patients to determine if there are any patterns in the genetic mutations and to learn more about the significance of various mutations. Dr. Aparicio said their work could help usher in an era in which scientists will be able to decode cancer genomes in every patient with the aim of devising therapies targeted to the mutations present in their tumours.
This also means patients may have to undergo numerous tests as their disease progresses to account for the fact that an individual's cancer goes though multiple changes over time.
A growing number of researchers have put stock in recent years in the idea that genome sequencing holds the key to understanding cancer development and creating targeted therapies. To date, the exorbitant cost and complex process of genome sequencing has put those lofty goals out of reach. But now a series of technological advancements has brought down the cost dramatically, which means the "possibility of obtaining genome sequence from every patient's tumour is coming closer," Dr. Aparicio said.
The scientists involved in this advance used next-generation DNA sequencing technology to decode the cancer genome, new technology that is lowering costs and helping to fuel genome-related research and discoveries around the world.
"We've been dreaming about the possibility to capture complete genome information from cancers in a routine way for decades," Dr. Aparicio said. "The moment has arrived."