Monthly Archives: October 2014

Scientists sequenced the genome of a man who lived 45,000 years ago
Scientists sequenced the genome of a man who lived 45000 years ago.

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A new comprehensive analysis of thyroid cancer from The Cancer Genome Atlas Research Network has identified markers of aggressive tumors, which could allow for better targeting of appropriate treatments to individual patients.

The finding suggests the potential to reclassify the disease based on genetic markers and moves thyroid cancer into a position to benefit more from precision medicine.

"This understanding of the genomic landscape of thyroid cancer will refine how it's classified and improve molecular diagnosis. This will help us separate those patients who need aggressive treatment from those whose tumor is never likely to grow or spread," says Thomas J. Giordano, M.D., Ph.D., professor of pathology at the University of Michigan Medical School.

Giordano is the project co-lead for TCGA thyroid cancer analysis along with Gad Getz, Ph.D., director of Cancer Genome Computational at the Broad Institute.

Thyroid cancer incidence has increased three-fold over the last 30 years and is the most rapidly increasing cancer in the United States. While the tumors are often slow-growing and easily treated with a combination of surgery, thyroid hormone and radioactive iodine, some patients will develop more aggressive and deadly thyroid cancers.

In this TCGA study, which is published in Cell, the researchers analyzed nearly 500 thyroid cancer samples to identify all genetic mutations that play a role. They found several new cancer genes as well as new variations of existing genes.

Overall, the thyroid cancer genome is relatively quiet, with fewer genetic mutations involved than in other common cancers, the researchers found. This may explain why the disease is often slow-growing.

Fewer mutations meant the researchers were able to look at the signaling pathways involved and understand what drives thyroid tumors. This approach helped them understand the genetic drivers of more of these cancers, reducing the percentage of "dark matter" cases -- those with unknown genetic drivers -- from 25 percent to 3.5 percent.

Those drivers can be broken down into two primary oncogenic groups: BRAF plus similar mutations and RAS plus similar mutations. But within these two primary groups, especially the BRAF group, several different subtypes of thyroid cancer exist. Currently, all thyroid cancers associated with BRAF, for example, had been considered essentially the same. That's not the case.

"This study integrated a wide variety of genomic data to not only identify cancer drivers, but to compare how these different drivers behave," said Getz, who is also director of the Bioinformatics Program at the Massachusetts General Hospital Cancer Center and an associate professor of pathology at Harvard Medical School. "Interestingly, we found that subsets of BRAF-mutated thyroid cancers are driving cancer through distinct mechanisms, and that some of these subsets are associated with higher risk and less differentiated cancers."

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Thyroid cancer genome analysis finds markers of aggressive tumors

Customized genome editing -- the ability to edit desired DNA sequences to add, delete, activate or suppress specific genes -- has major potential for application in medicine, biotechnology, food and agriculture.

Now, in a paper published in Molecular Cell, North Carolina State University researchers and colleagues examine six key molecular elements that help drive this genome editing system, which is known as CRISPR-Cas.

NC State's Dr. Rodolphe Barrangou, an associate professor of food, bioprocessing and nutrition sciences, and Dr. Chase Beisel, an assistant professor of chemical and biomolecular engineering, use CRISPR-Cas to take aim at certain DNA sequences in bacteria and in human cells. CRISPR stands for "clustered regularly interspaced short palindromic repeats," and Cas is a family of genes and corresponding proteins associated with the CRISPR system that specifically target and cut DNA in a sequence-dependent manner.

Essentially, the authors say, bacteria use the system as a defense mechanism and immune system against unwanted invaders such as viruses. Now that same system is being harnessed by researchers to quickly and more precisely target certain genes for editing.

"This paper sheds light on how CRISPR-Cas works," Barrangou said. "If we liken this system to a puzzle, this paper shows what some of the system's pieces are and how they interlock with one another. More importantly, we find which pieces are important structurally or functionally -- and which ones are not."

The CRISPR-Cas system is spreading like wildfire among researchers across the globe who are searching for new ways to manipulate genes. Barrangou says that the paper's findings will allow researchers to increase the specificity and efficiency in targeting DNA, setting the stage for more precise genetic modifications.

The work by Barrangou and Beisel holds promise in manipulating relevant bacteria for use in food -- think of safer and more effective probiotics for your yogurt, for example -- and in model organisms used in agriculture, including gene editing in crops to make them less susceptible to disease.

The collaborative effort with Caribou Biosciences, a start-up biotechnology company in California, illustrates the focus of these two NC State laboratories on bridging the gap between industry and academia, and the commercial potential of CRISPR technologies, the researchers say.

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The above story is based on materials provided by North Carolina State University. Note: Materials may be edited for content and length.

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Genome editing technique advanced by researchers