A team from the University of Cambridge has found that four-stranded DNA structures—known as G-quadruplexes—play a role in certain types of breast cancer. G-quadruplexes form in regions of DNA that are rich in guanine, when a single strand of the double-stranded DNA loops out and doubles back on itself, forming a four-stranded 'handle' in the genome.

The team, led by Professor Balasubramanian, had previously developed sequencing technologies and approaches capable of detecting G-quadruplexes in DNA and in chromatin. They also previously found that G-quadruplexes play a role in transcription and that G-quadruplexes are more likely to occur in genes of cells that are rapidly dividing, such as cancer cells.

In the new study, the team has discovered where G-quadruplexes form in preserved tumor tissue/biopsies of breast cancer. Details of their study were published today in Nature Genetics.

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Using their quantitative sequencing technology to study G-quadruplex DNA structures in 22 model tumors, the researchers found that G-quadruplexes are prevalent within copy number aberrations (CNAs), particularly within genes and genetic regions that play an active role in transcription and hence in driving the tumor's growth.

"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," explained Robert Hänsel-Hertsch first author on the publication.

"Importantly, it highlights another potential weak spot that we might use against the breast tumor to develop better treatments for our patients," he added.

By targeting the G-quadruplexes with synthetic molecules, it may be possible to prevent cells from replicating their DNA and so block cell division, halting the runaway cell proliferation at the root of cancer. The team identified two such molecules—one known as pyridostatin and a second compound, CX-5461, which has previously been tested in a phase I trial against BRCA2-deficient breast cancer.