Canadian researchers show how a breast tumor evolves

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For the first time, Canadian researchers have decoded the DNA of breast cancer cells when the tumor was localized and after it had spread, providing previously unavailable information about how changes in DNA lead to metastasis and yielding some insight into why many forms of therapy sometimes fail. The achievement also represents a scientific tour de force, providing three complete DNA sequences for the patient in a matter of weeks and at an affordable cost. As recently as 20 years ago, researchers were estimating that decoding a single human genome would require 10 years of work and cost $3 billion. Now that they have worked out the technology, the researchers say they are deciphering several genomes each week.

Dr. Samuel Aparicio, an oncologist an the British Columbia Cancer Agency, and his colleagues sequenced DNA from a breast tumor in a woman who had been newly diagnosed with a lobular breast cancer and compared it with a DNA sequence obtained nine years later and to one from healthy tissue from the same woman, a feat that had never been accomplished before.

They reported today in the journal Nature that the DNA from the metastasized tumor contained 32 mutations that were not present in the healthy tissue. DNA from the localized tumor contained five mutations that were not in the healthy tissue. Many of the mutations--including all five in the original tumor--had not previously been recognized, and their discovery may open the door to a better understanding of how the tumor forms in the first place and what changes it must go through to spread. Some of the mutations, probably, are simply so-called carrier mutations that do not affect the tumor’s ability to spread, and the challenge will be to decide which are which.

Intriguingly, six of the mutations were present only in a subset of metastatic cells, suggesting that the tumor cells are heterogeneous. That could potentially have implications for therapy, Aparicio said, because one set of cells may be susceptible to one drug and the second set only to other drugs.

Aparicio said he plans to sequence tumors from an additional 250 women over the next year to see if similar changes are involved in all of them, or if different patterns of mutation arise.

-- Thomas H. Maugh II