Four-Stranded DNA Structures Identified in Breast Cancer Cells
Posted: Thursday, October 15, 2020
A recent study published in Nature Genetics by Shankar Balasubramanian, MA, MSci, PhD, of the University of Cambridge, and colleagues, has shown for the first time the existence of four-stranded DNA in human breast cancer cells. Their research findings suggest potential clinical implications for both the diagnosis and management of breast cancer.
“The abundance and location of G-quadruplexes in these biopsies gives us a clue to their importance in cancer biology and to the heterogeneity of these breast cancers,” commented the first author of the study, Robert Hänsel-Hertsch, PhD, in Genetic Engineering & Biotechnology News. He is now at the Center for Molecular Medicine Cologne, University of Cologne.
In this study, the researchers examined G-quadruplex DNA structure-forming regions in 22 patient-derived tumor xenograft mouse models. Of them, 14 were found to associate with more than one breast cancer subtype, suggesting that multiple breast cancer states frequently coexist within a tumor. The researchers also found that G-quadruplexes were most commonly found in promoter regions of highly amplified genes that showed high expression and that the majority of the tumors displayed aggressive triple-negative [integrative cluster 10]-related breast cancer gene activity.
Using quantitative G-quadruplex chromatin-immunoprecipitation sequencing, the researchers showed that G-quadruplex DNA regions were highly associated with drivers of triple-negative breast cancer and/or integrative cluster 9-10. They found that G-quadruplex structure-forming regions were associated with at least seven distinct transcription factor programs, suggesting that many transcription factors work together to regulate breast cancer gene activity.
“[G-quadruplex DNA structure-forming regions], in combination with established knowledge on subtypes, can refine the genomic transcriptomic and regulatory classification of breast cancer. Finally, [G-quadruplex] levels in cancer models are sufficient to predict response to treatment by small molecules that target [G-quadruplex] DNA structures, which highlights [G-quadruplexes] as genomic features with potential for future diagnostics and therapeutics,” the authors concluded.
Disclosure: For full disclosure of the study authors, visit nature.com.
