Hominid
08-10-2009, 15:38
Canadian scientists have become the first in the world to decode the DNA of breast cancer cells, and have discovered, to their surprise, that the gene mutations in those tumours shift as the disease spreads.
The finding brings researchers unprecedented information about how breast cancer progresses and shows that the disease is a moving target that often changes the way it operates.
"I never thought I would see it in my lifetime," co-principal investigator Dr. Samuel Aparicio, head of the agency's breast cancer research program, said of the discovery.
The research is the cover story in this week's issue of the prestigious journal Nature.
Researchers with the B.C. Cancer Agency say they made their discovery after decoding the entire genome of a patient's metastatic breast cancer and finding all the genome's mutations.
Genetic mutations are often harmless, but when mutations appear in the genes that control cell division, that can cause cells to grow in an uncontrolled way, which is how cancer develops.
What cancer researchers haven't been able to do until now is to find all of the mutations present in a given tumour. But now, by sequencing the tumour's DNA, the B.C. researchers have uncovered some remarkable discoveries.
In the patient they studied, they found 32 mutations in a breast cancer tumour that had metastasized, or spread, nine years after the original diagnosis. The team then looked to see how many of these mutations were in the original breast tumour at the time of diagnosis.
To their surprise, they found that only 11 of the 32 mutations were in the original tumour, implying that considerable evolution had taken place within the cancer cells over time, during and after therapy.
Moreover, of the 11 mutations found in the original primary tumour, only five could have been present in all of the tumour cells. Six mutations were present in only a fraction of the cells.
This is a fundamental observation showing that right from the outset, not all of the cells of the breast cancer contained the same mutations. Until now, it had been assumed that tumours have the same mutations in the DNA sequence of all cells.
The discovery might explain why treatments that work for some women fail on others, or why a treatment for a primary tumour fails when the cancer returns.
Aparicio says the discovery will change the way researchers think about which patients will benefit the most from which treatments, and says the work is another major step towards personalized medicine.
He said there are big implications for the making of new cancer drugs, which may be designed to deal with the various mutations.
"What the new approaches are leading us to now look at are can we associate mutations in the tumours with the response to drugs?"
While it took the international human genome consortium eight years and several billion dollars to decode the first human genome back in 2001, the B.C. team decoded the breast tumour DNA in a matter of weeks and at a fraction of the cost, using the latest DNA sequencing technology at the B.C. Cancer Agency's Michael Smith Genome Sciences Centre
Researchers are now building a genomic map of breast cancer based on 2,000 cancers.
They are also focusing on sequencing the genomes of so-called "triple negative" breast cancers, which are particularly aggressive and for which there are far fewer treatment options than for other breast cancers.
bron
The finding brings researchers unprecedented information about how breast cancer progresses and shows that the disease is a moving target that often changes the way it operates.
"I never thought I would see it in my lifetime," co-principal investigator Dr. Samuel Aparicio, head of the agency's breast cancer research program, said of the discovery.
The research is the cover story in this week's issue of the prestigious journal Nature.
Researchers with the B.C. Cancer Agency say they made their discovery after decoding the entire genome of a patient's metastatic breast cancer and finding all the genome's mutations.
Genetic mutations are often harmless, but when mutations appear in the genes that control cell division, that can cause cells to grow in an uncontrolled way, which is how cancer develops.
What cancer researchers haven't been able to do until now is to find all of the mutations present in a given tumour. But now, by sequencing the tumour's DNA, the B.C. researchers have uncovered some remarkable discoveries.
In the patient they studied, they found 32 mutations in a breast cancer tumour that had metastasized, or spread, nine years after the original diagnosis. The team then looked to see how many of these mutations were in the original breast tumour at the time of diagnosis.
To their surprise, they found that only 11 of the 32 mutations were in the original tumour, implying that considerable evolution had taken place within the cancer cells over time, during and after therapy.
Moreover, of the 11 mutations found in the original primary tumour, only five could have been present in all of the tumour cells. Six mutations were present in only a fraction of the cells.
This is a fundamental observation showing that right from the outset, not all of the cells of the breast cancer contained the same mutations. Until now, it had been assumed that tumours have the same mutations in the DNA sequence of all cells.
The discovery might explain why treatments that work for some women fail on others, or why a treatment for a primary tumour fails when the cancer returns.
Aparicio says the discovery will change the way researchers think about which patients will benefit the most from which treatments, and says the work is another major step towards personalized medicine.
He said there are big implications for the making of new cancer drugs, which may be designed to deal with the various mutations.
"What the new approaches are leading us to now look at are can we associate mutations in the tumours with the response to drugs?"
While it took the international human genome consortium eight years and several billion dollars to decode the first human genome back in 2001, the B.C. team decoded the breast tumour DNA in a matter of weeks and at a fraction of the cost, using the latest DNA sequencing technology at the B.C. Cancer Agency's Michael Smith Genome Sciences Centre
Researchers are now building a genomic map of breast cancer based on 2,000 cancers.
They are also focusing on sequencing the genomes of so-called "triple negative" breast cancers, which are particularly aggressive and for which there are far fewer treatment options than for other breast cancers.
bron