Although gene-reading technology is advanced and sophisticated, there are certain parts of DNA that it does not cope with perfectly; for instance, there are repetitive areas of DNA that cause the machinery to “stutter.” But there is a way to examine these “blind spots” and discover if they conceal cancer genes.
This was the conclusion of a new study by Cancer Research UK scientists working at The University of Manchester in the UK, who report their findings in the journal Cancer Research.
The team found more than 400 blind spots in DNA that could be harboring cancer-causing gene faults, as lead researcher Andrew Hudson, a clinical fellow at the Cancer Research UK Manchester Institute explains:
“The genes behind cancer are like a story. While we’ve been able to read most of the book using gene-reading technology, the limits of these tools mean some pages are missing.”cancer
To look for “missing pages,” the team compared two prominent cancer genome sequencing databases that got their information from studies of lab-grown cancer cells, and they cross-checked all the genes that are known or suspected to be involved in cancer to locate any discrepancies.
They write how their analysis “revealed marked discrepancies in the detection of missense mutations in identical cell lines (57.38% conformity),” and they note that the main reason for the discrepancy “is inadequate sequencing of GC-rich areas.”
In other words, for certain regions of DNA, there was over 40% mismatch in the code sequence given by the two databases, even though the information came from identical cell lines. The authors note these mismatches occurred in “GC-rich” areas of DNA. GC stands for guanine and cytosine, two of the four building blocks of DNA.
Also, as a “proof of principle” to show that it is worth looking more closely at the blind spots for new cancer drivers, the team focused on a newly identified mutation in the PAK4 gene. They showed that “specific targeting and sequencing” of the GC-rich blind spots “can lead to the identification of novel driver mutations in known tumor suppressors and oncogenes.”
They conclude that their study shows by cross-referencing between gene databases of commonly used cell lines, it is possible to discover new drivers of cancer – by looking in the poorly sequenced areas.
Nell Barrie, senior science information manager for Cancer Research UK says:
“By delving deeper into cancer’s genetic origins we can spot the ways the disease is triggered and develops. This could help us to tackle it from the root, giving more cancer patients a chance at surviving the disease.”
In October 2014, Medical News Today learned how insights into how cells copy chromosomes could be important for fighting cancer. A team of researchers discovered if a component for unwinding DNA strands remains intact after chromosome copying is complete, it can play havoc with cell division, a known trigger for cancer.