Early chromosome changes a potential target in triple-negative breast cancer

MD Anderson scientists found that chromosomal changes in triple-negative breast cancer occur early on and in short “bursts,” contradicting the long-standing belief that they occur slowly over time in many cancers. This could lead to more effective diagnostic and treatment strategies for triple-negative breast cancer.

The team used highly multiplexed single-nucleus sequencing to delve into the clonal substructure and evolution of CNAs in 12 triple-negative breast cancer patients who had had their tumors surgically removed ahead of further therapy. With this new sequencing method, they were able to sequence the genomes of individual tumor cells and study numerous cells simultaneously.

“The current model asserts [DNA copy number aberrations, or CNAs] are acquired gradually and sequentially over extended periods of time, leading to successively more malignant stages of cancer,” said Nicholas Navin, a professor of genetics at the MD Anderson Cancer Center, in a statement. “Another model is punctuated evolution in which CNAs are acquired in short bursts of crisis, followed by stable clonal expansion that form the tumor mass. Our study suggests punctuated copy number evolution is common in TNBC patients.”

Previous genomic studies have focused on a snapshot in time, after the tumor has been removed, the researchers said in the statement. Therefore, it has been challenging to examine the history of how chromosomes evolve in cancer.

And the “bursts” may have applications beyond triple-negative breast cancer. “Our preliminary data in cancers such as prostate, colon, liver and lung suggest a punctuated model of copy number evolution is also likely to be operative in other solid cancers,” Navin said. “This model has important implications for our evolutionary understanding of cancer growth dynamics and for the clinical diagnosis and treatment of TNBC patients.”

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