In 1953, scientists Francis Crick and James Watson showed that DNA has an intertwined, double helix structure. The DNA is the hereditary material in all living organisms located in the cell nucleus.
After 60 years since that discovery, Cambridge professors Sir Shankar Balasubramanian and Steve Jackson found an unusual four-stranded DNA structure that can occur across the human genome.
These four-stranded DNA structures, known as G-quadruplexes, play a role in certain types of breast cancers, providing possible weak spots that scientists can use in developing cancer treatments.
Four-Stranded DNA Found In Breast Cancer Cells Can Provide Weak Spots For Developing New Treatments
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G-quadruplexes: The four-stranded DNA
G-quadruplexes are formed in regions of the DNA, rich in one of its building blocks, guanine (G). They are created when one strand of the double-stranded DNA loops out and doubles back on itself.
Professor Balasubramanian and his colleagues detected these structures in DNA and chromatin using sequencing technologies and approaches. They have previously shown that G-quadruplexes play a role in transcription, an essential step in reading the genetic material and generating proteins from the DNA.
More so, the researchers said that G-quadruplexes are present in rapidly dividing cancer cells. For the first time, they discovered where it forms in the preserved tumor tissues from biopsies of breast cancer. They published their results in the journal Nature Genetics.
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G-quadruplexes in Cancer Cells
To study G-quadruplex DNA structures in 22 model tumors, professors Balasubramanian and Caldas used their quantitative sequencing technology. These tumor tissues were from biopsies from patients at Addenbrooke's Hospital and were then transplanted into mice to allow them to grow.
The researchers discovered that G-quadruplexes are present in the copy number aberrations (CNAs), more specifically in the regions that play an active role in transcription that drives tumor growth. CNAs are created when genomes during cell division in cancer cells are erroneously duplicated several times.
Professor Balasubramanian noted that this is the first time that four-stranded DNA structures are found in breast cancer cells. Its presence in the region gives scientists a clue to cancer biology, added Dr. Robert Hänsel-Hertsch.
But most importantly, it highlights another potential weak spot that doctors can use against breast tumors, in developing treatments for breast cancer patients.
There are at least 11 subtypes of breast cancer, and professor Balasubramanian and his colleagues found specific G-quadruples unique to each subtype.
"Identifying a tumor's particular pattern of G-quadruplexes could help us pinpoint a woman's breast cancer subtype, enabling us to offer her a more personalized, targeted treatment," said Professor Carlos Caldas from the Cancer Research UK Cambridge Institute.
It may be possible to prevent cancer cells from replicating and block cell division by targeting the four-stranded DNA structures with synthetic molecules.
The researchers identified two synthetic molecules: pyridostatin and the second compound is called the CX-5461, previously tested in a phase I trial against the BRCA2-deficient breast cancer.
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