Next Generation Sequencing

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Next Gen Sequencing When President Obama launched the Precision Medicine Initiative in 2015, the goal was to make treatment options better by focusing on a new approach – one that takes into account a person’s individuality by noting details such as variations in genes, lifestyle and environment. Moving into this era of medicine has been no easy feat; however, we are seeing progress. On July 6, 2016, the FDA drafted guidelines on next generation sequencing (NGS) to help move precision (or personalized) medicine forward. But what is next generation sequencing? Sounds a bit sci-fi, straight out of Star Trek: The Next Generation. Truth be told, the future of medicine is closer than we think! FightCRC_NextGenSequencing1

What is NGS?

Next Generation Sequencing has the ability to read a person’s DNA code to detect genomic variations, or mutations, that could determine if that person is at risk for a particular disease, such as diabetes or cancer. Knowing the genomic mutations present may also determine what treatment option is best for you.

The terminology

Genes are units of heredity that we get from our parents. They give us particular characteristics – for example, they predict hair and eye color. Specific sequences of genes make up DNA on a single chromosome. Finally, a genome is a person (or organism’s) full set of genes and gene-modifiers. A genome is sort of like a recipe book, however, no person has the exact, same combination of genetic details. Everyone is unique.

A brief history of gene sequencing

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Fred Sanger developed the "Sanger Sequencing Method" used for 25 years that set the stage for the Human Genome Project
The first DNA genome to be sequenced was a virus, and the project was completed in 1977 by Fred Sanger. The Sanger Sequencing Method, as it’s known, was the main method used for over 25 years. It’s still used today, in some instances. It’s especially used to look for mutations in a single suspect gene in a patient’s tumor, for example. It set the stage for the Human Genome Project. The next generation of sequencing methods (NGS) began to emerge in 2005. This new technology is faster than Sanger’s Method, with more precise results. In fact, NGS can take as little as one day to one week, whereas previous techniques took years. NGS identifies millions of genetic variations at a time and this, according to the FDA, is why they require oversight. With such amazing technical advancements, the FDA hopes to evaluate clinical validity (how well the test detects disease or a condition) of the new technology, and also analytic validity (is the test truthful and accurate in what it is supposed to do?). We asked John Tentler, Ph.D, a cancer researcher at the CU Anschutz Medical Campus, his thoughts about next generation sequencing, to which he replied:
“If these tests prove to be valid it will revolutionize how cancer is diagnosed, treated, and perhaps most importantly, how resistance develops to current therapies so that we can stay one step ahead of the cancer with effective new treatments.”
Dr. Tentler currently uses Next Generation Sequencing to guide his research into novel cancer therapies.  

Recent FDA drafts

To elevate the work of the PMI’s mission of individualized care, two drafts were written with input from industry partners, health care providers, patient groups, professional societies, NGS test developers and experts in genomics. They encompass the FDA’s commitment to harnessing technology and sharing of new genetic and genomic findings. Once these documents (currently in review) are finalized, they’re intended to help inform how the tests are made and used. This is the FDA’s way of acknowledging next generation sequencing, and an attempt to streamline and encourage advancements in a safe and effective way. Once finalized, the drafts will remain as recommendations – not guidelines – to be consulted by researchers and developers who make these amazing, not-so-futuristic tests. FightCRC_NextGenSequencing2

What does this mean for CRC patients?

No cancer is the same – there are complexities within tumor genomes and also at the molecular level, from patient to patient, that are showing a bigger, more personalized picture for each patient with cancer. Colorectal cancer has a few identified genetic-based biomarkers such as mutations that can be found within genes, or genomes. The biomarkers are either predictive or prognostic. Predictive means the biomarkers can anticipate whether or not someone will have a positive response to a particular treatment; prognostic identifies the aggressiveness of the individual’s cancer. For more information, check out Dr Tentler’s guest blog from earlier this year or download our biomarkers fact sheet. Because high-speed genetic sequencing of tumors is now available, research is moving forward more rapidly than before. The ability to identify mutations within tumors will allow researchers to understand better treatment options and the development of new medicines like therapeutic cancer vaccines. Now that researchers, scientists and others in the field are able to sequence a cancer genome more quickly and cost efficiently than in the early Sanger days, research can proceed to discover innovative ways to treat colorectal cancer on an tailor-made, individual level.

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Additional Resources:

Next-generation sequencing for genetic testing of familial colorectal cancer syndromes Sanger, F, Micklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. PNAS 1977; 74:5463-5467. Collins FS, Morgan M, Patrinos A. The human genome project: lessons from large-scale biology. Science. 2003;300:286-290.