Gene mutation ‘hotspots’ linked to better cancer outcomes, researchers say

Breast cancer patients with groups of mutations clustered in their genome have better outcomes than patients without them, researchers found in a recent study.

More than half of breast cancer patients have clusters of genetic mutations called kataegis, and their cancer tends to be less invasive, offering better opportunities for effective treatment, according to researchers at the University of California San Diego.

The researchers say they are unsure of the causes of kataegis, but experiments have shown genes located near the mutation hotspots are less likely to behave abnormally than those farther away. Previous studies have associated the phenomenon with pancreatic cancer, lymphoma, leukemia and lung cancer, in addition to breast cancer.

The mutations also appear to be linked to higher levels of human epidermal growth factor 2 and elevated levels of an immunotherapy target for gastric cancer — suggesting patients with kataegis have options for treatment known to be highly effective against the disease.

“We think kataegis mutations are dampening the abnormal expression of neighboring genes that might otherwise contribute to tumor development and invasiveness,” Dr. Matteo D’Antonio, a postdoctoral researcher at the University of California San Diego, said in a press release.

For the study, published in the journal Cell Reports, researchers established kataegis status for 97 breast cancer patients, and predicted it for another 412, based on genomic data collected by the National Institutes of Health’s Cancer Genome Atlas.

After matching kataegis status with specific patient data — age at diagnosis, treatment and outcome — the researchers found the mutations are more common in breast cancer patients diagnosed later in life, as well as those with HER2-positive and high-grade tumors.

Patients without the mutations were found to die at a median of 47 years old, while those with them died at a median age of 78, the researchers report.

In terms of treatment, tumors with kataegis tend to be higher in HER2, meaning treatment targeting the growth factor will respond more positively. Tumors with the mutations also had higher levels of the PLAC1 gene, an immunotherapy target for gastric cancer, suggesting immunotherapy drugs also could be more effective for patients with the clusters of mutations.

“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,” said Dr. Kelly Frazer, a professor of pediatrics and director of the Institute for Genomic Medicine at UC San Diego School of Medicine. “We’ve now found that kataegis is associated with a good prognosis for patients with breast cancer.”