Study Finds ‘Bursts’ of Chromosome Changes Fuel Breast Cancer Tumor Growth
As with most cancers, triple-negative breast cancer cells have abnormal amounts of chromosomes or DNA copy number aberrations in their genomes. A new study used single-cell sequencing technology to provide previously unknown details about how and when copy number aberrations impact tumor formation and growth, information that may have significant implications for diagnosis and treatment.
The research results, published by Gao et al in Nature Genetics, challenge the prevailing belief that copy number aberrations take place slowly and gradually over time. Instead, study findings revealed chromosomal changes occur in short, punctuated “bursts” at the earliest stages of tumor growth.
“The current model asserts [copy number aberrations] are acquired gradually and sequentially over extended periods of time, leading to successively more malignant stages of cancer,” said Nicholas Navin, PhD, Professor of Genetics at The University of Texas MD Anderson Cancer Center and lead author of the paper. “Another model is punctuated evolution in which [copy number aberrations] 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 [triple-negative breast cancer] patients.”
Study Implications
The study supports the “bursts” model and demonstrates the majority of copy number aberrations are acquired at the earliest stages of tumor evolution. The discovery is important, since most genomic studies have focused on a single point in time: after a tumor has been surgically removed, making it difficult to study the natural history of chromosome evolution during tumor growth.
The finding also indicated other cancers may demonstrate similar copy number aberration behavior.
“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,” said Dr. Navin. “This model has important implications for our evolutionary understanding of cancer growth dynamics and for the clinical diagnosis and treatment of [triple-negative breast cancer] patients.”
The research team developed a new method called highly multiplexed single-nucleus sequencing to investigate the clonal substructure and evolution of copy number aberrations in a cohort of 12 triple-negative breast cancer patients, whose tumors had been surgically removed prior to further therapy. Highly multiplexed single-nucleus sequencing allows researchers to sequence the genomes of single tumor cells and study multiple cells simultaneously, both lowering the cost and boosting data analysis for such studies.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
