Oncologists may now have a better way to classify – and ultimately treat – breast cancer.
Researchers out of the Mayo Clinic in Jacksonville, Fla., have uncovered a new class of molecular mutations in breast cancer tissue – a discovery that could lead to a better understanding of how to provide individualistic treatment for the disease.
The mutations are called fusion transcripts and are formed when chromosomes break apart and fuse together to become fusion genes. Fusion genes – comprised of DNA – subsequently produce fusion transcripts (RNA).
“We found 131 fusion transcripts, but what made it more interesting was that 45 of those transcripts were seen in multiple specimens,” said Dr. Edith Perez, deputy director of the Mayo Clinic Comprehensive Cancer Center in Florida and senior investigator for the study. “When we looked at the expression of these noble fusion transcripts, they appeared to be subtype-specific.
Currently, oncologists are aware of three basic categories of breast cancer – estrogen-receptor (ER)-positive, HER2-positive, and triple negative.
After collecting cancer cells from 24 different breast cancer tumors and comparing them to non-cancer cells, Perez and her team found that certain types of fusion transcripts would appear multiple times in the same cancer subtypes. For example, one kind of transcript would appear over and over in triple negative cancer cells, while another kind of transcript would appear repeatedly in HER2-positive cancer cells – making them subtype-specific.
By observing this repetition of fusion transcripts, the team potentially identified the fused RNA as biomarkers that can be used to help treat the disease in the future.
“These transcripts represent a previously underappreciated class of genetic features that may have considerable potential as biomarkers or therapeutic markers in breast cancer,” Perez said.
Fusion transcripts are typically formed in cancer cells and have recently become helpful biomarkers for common blood cancers such as leukemia and lymphoma. This discovery is one of the first to reveal fusion transcripts in solid cancers – and the first to reveal transcripts in breast cancer tissue.
“The techniques that we are using to harvest these gene products are brand new,” Perez said of how they found the transcripts. “We developed a new way to do the statistical analysis to understand what the information means, and we now have the clinical expertise to put all this together.”
After their novel discovery, the researchers hope to better identify the role these fusion transcripts play during breast cancer progression.
“Now we’re going to understand the functional significance of these fusion transcripts. Perez said. “We feel that it may be the case that these fusion transcripts are involved in the development of the cancer. Suddenly these genes decided to fuse and that could be associated in cancer growth.”
As many doctors search for a much more individualized approach to treating cancers in their patients, Perez and her team’s discovery have paved the way for a better understanding of both the origin of breast cancer and how to eventually terminate it.
“That’s what’s next for us. Can we identify new targets to be used to develop drug treatments as well as new ways to sub-classify breast cancer and why it develops?”
“We now have this outline for the future,” Perez said.
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