DNA and RNA Sequencing Provides Insights into How Breast Cancer Metastasizes

DNA and RNA Sequencing Provides Insights into How Breast Cancer Metastasizes

Researchers at the University of North Carolina Lineberger Comprehensive Cancer Center have discovered genetic clues that could explain how breast cancer metastasizes.

While breast cancer can be treated if caught early, the majority of deaths from the disease occur when the cancer spreads to other parts of the body. Knowing how the disease spreads could help researchers develop more effective treatments for the disease, or at least develop new approaches that could reduce the potential for the disease to spread.

The researchers conducted an analysis of DNA and expression patterns in primary tumors and metastatic tumors in 16 patients using data taken from the UNC-Chapel Hill Breast Cancer Tumor Donation Program. The researchers identified genetic differences in primary tumors and metastatic cancers providing some insight into the evolution of cancers.

The research showed that in most cases, metastases were not due to the spread of a single cell, instead multiple cells likely broke away from the primary tumor. The researchers note that in patients with metastatic cancers, the genetic diversity in those cancers reflects the genetic diversity in the primary tumor.

The researchers suggest that there may be different genes driving metastasis. If that is the case, this has implications for treatment. If metastatic cancers are made up of different cells with different genetic drivers, treatment of the primary tumor should involve multiple drugs that target those different drivers. This could help to prevent metastasis.

The researchers also discovered that the genetic drivers linked to the aggressiveness of the tumor were also found in the metastatic cancers and that the genes that caused the primary cancer were also involved in the metastatic process. The research suggests that new traits do not need to be acquired to allow the cancer to spread to multiple sites.

By carefully analyzing the primary tumor it may be possible to obtain the information needed to prevent metastases. “If you can get a better handle on the biology of the primary tumor, and the elements of the tumor that may be more or less dangerous, then you don’t need to worry about testing every single metastasis for treatment decisions,” said UNC Lineberger’s Lisa A. Carey, MD.

The team discovered that most of the genetic alterations in both primary tumors and metastases were copy number alterations. “We saw frequent copy number changes, and gene expression changes in metastases that reflect a change in metabolism,” said Marni Siegel, first author of the study. “These tumors are genetically very complex, and we demonstrated this by showing just the sheer volume of copy number changes, and that there are multiple clones in a single metastases tumor, and changes in metabolism that reflects the tumor’s ability to adapt.”

There was also notable genetic variation between different metastases in the same patient. The researchers suggest there may be site-specific resistance mechanisms. “Being able to understand what came from the original tumor and what happened only in the metastases is key to improving treatment,” said Carey Anders, MD, co-senior author of the paper and medical director of the UNC Breast Center.

The research is detailed in the paper – Integrated RNA and DNA sequencing reveals early drivers of metastatic breast cancer – recently published in the Journal of Clinical Investigation.

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