Research on kataegis — clusters of mutations in some hotspots in a genome — is revealing that the phenomenon plays a positive role in breast cancer by rendering tumors less invasive and offering patients a better prognosis.
Kataegis, the ancient Greek word for thunder, had been studied in breast cancer but researchers only recently determined if the thunderstorm of mutations are bad or good news.
The study, “Kataegis Expression Signature in Breast Cancer Is Associated with Late Onset, Better Prognosis, and Higher HER2 Levels,” was published in the journal Cell Reports.
In a press release, senior study author Kelly Frazer, a professor of pediatrics and director of the Institute for Genomic Medicine at University of California, San Diego School of Medicine and Moores Cancer Center, confirmed findings.
“We don’t know what causes kataegis, and before this study not much was known about its functional importance at the molecular or clinical level,” Frazer said. “We’ve now found that kataegis is associated with a good prognosis for patients with breast cancer.”
Earlier studies showed that kataegis is present in about 55 percent of all breast cancers. Using available data from The Cancer Genome Atlas (TCGA), a National Institutes of Health’s database with genetic profiles of more than 15,000 human tumors of various sorts, the research team identified 97 tumors with kataegis.
Data for each tumor was linked to patient information on diagnosis, treatment and outcomes; which made it possible for the team to link factors.
Using the data from the initial 97 tumors, the team built a statistical model that could predict the presence of kataegis in an additional 412 breast cancers where the presence of kataegis was not known.
The data showed that kataegis was frequently found in women falling ill at a later ages, as well as in patients with tumors positive for HER2 (human epidermal growth factor receptor 2) or in tumors poorly resembling the tissue from which they originate.
Tumors with kataegis, particularly those located on chromosome 17 and 22 were less invasive – and patients had a life expectancy of up to 40 years longer.
“We think kataegis mutations are dampening the abnormal expression of neighboring genes that might otherwise contribute to tumor development and invasiveness,” said Matteo D’Antonio, a first author of the study.
Additional benefits to having the mutation hot-spots were also found. Tumors with kataegis produce high levels of HER2, making them suitable for certain therapies. And the tumors express a gene targeted by an immunotherapy treatment for gastric cancer, which opens the possibility of using the therapy also for breast cancer.
Frazer predicts that kataegis will likely not be used in a clinical setting for some time, although Moores’ doctors have already begun to use genetic profiles of cancers to tailor treatments to individual patients.