'Blind spots' in DNA may conceal cancer genes

Date: Nov-17-2014 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.

The researchers employed two huge cancer gene databases to locate blind spots in DNA that may contain cancer-causing 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."

"These pages could just be unimportant filler," he adds, "but we wonder if they

might hold important twists in the plot which could affect our

understanding of cancer. The next step in our work will be to find a

way to open up these areas to help piece together the full story."

The team compared two huge cancer gene databases

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.

The two databases they used are the CCLE, the Cancer Cell Line Encyclopedia and COSMIC, the Catalogue of Somatic Mutations in

Cancer.

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.

'Delving deeper into cancer's genetic origins' to find disease

triggers

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.

Written by Catharine Paddock PhD

Not to be reproduced without permission.

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Courtesy: Medical News Today Note: Any medical information available in this news section is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional.