A study published recently in Nature Genetics, carried out by a multi-institutional group of researchers led by the Princess Margaret Cancer Center (ON, Canada), has identified additional noncoding genetic drivers of estrogen-receptor (ER)-positive breast cancer.
In approximately two-thirds of cases, ER-positive breast cancer is characterized by the sustained expression of the ER-α (ESR1), making this receptor the most frequently utilized biomarker and therapeutic target for ER-positive disease.
Genetic mutations fuelling ESR1 expression in ER-positive breast cancer have been studied extensively, therefore, in this study the team aimed to look beyond genetic mutations. Utilizing epigenetics, the team observed a significant number of somatic mutations in a set of regulatory elements that have previously been demonstrated to regulate ESR1 expression in 7% of ER-positive breast cancers.
Lead author Mathieu Lupien (Princess Margaret Cancer Centre) commented: “By investigating acquired mutations found outside of genes through the power of epigenetics, we have identified that functional regulatory components can be altered to impact the expression of genes to promote breast cancer development.”
Lupien believes that this research highlights the importance of viewing the combined activity of regulatory elements as a single unit in order to fully appreciate the impact that noncoding genetic alterations can have on single genes in ER-positive breast cancer.
He concluded by stating: “We now have the opportunity to start mining the genome for driver mutations not only in genes but also in other functional regulatory components to expand our capacity to identify the best biomarkers and to delineate the fundamental biology of each tumor to help advance personalized cancer medicine for patients.”
Sources: Bailey SD, Desai K, Kron KJ et al. Noncoding somatic and inherited single-nucleotide variants converge to promote ESR1 expression in breast cancer. Nat. Genet. doi: 10.1038/ng.3650 (2016); University Health Network press release