From the Precision Medicine Initiative and Vice President Biden’s Cancer Moonshot to nutrition and fitness, genomics is playing an increasing role in how we approach medicine and health. Last month, the Department of Health and Human Services’ Office of the Assistant Secretary for Preparedness and Response announced an initiative to advance a next-generation gene sequencing platform through ASPR’s Biomedical Advanced Research and Development Authority.
The goal is to speed up decoding DNA and RNA fast enough to respond to major public health threats like pandemic flu outbreaks and antibiotic-resistant infections.
Genomics is now a standard of care in noninvasive prenatal testing, where the accuracy rate is 99%. A study this summer in the journal Neurology showed that genetic variants linked to Alzheimer’s disease can predict a person’s risk years before dementia sets in. These are not the only two areas in which genomics is making waves.
Transforming cancer care
Earlier this year, Genomic Data Commons signed a data-sharing agreement between the National Cancer Institute and molecular information company Foundation Medicine to expand the patient database from 18,000 to about 32,500 adults. Also, IBM Watson Health, Quest Diagnostics and Memorial Sloan Kettering Cancer Center launched a genomic sequencing service in October to bring precision cancer treatments to patients across the U.S.
The three-way collaboration combines IBM Watson’s data processing and analytics capabilities with MSK’s cancer expertise and Quest’s ability to generate the sequencing data and really have it utilized in communities outside of academic medical centers where most of the tumor sequencing and targeted therapies take place today.
This could be groundbreaking since 70% of people with cancer are treated by community oncologists, says Jay Wohlgemuth, chief medical officer at Quest Diagnostics. The company interfaces with about 50% of doctors and hospitals in the country, with EHR connections, health IT tools and genetic counseling to help patients understand the results of genetic tests.
In the case of cancer, mutations in the DNA of a tumor have been shown to strongly correlate with a likely response to therapy. “What we’re looking for in most cases is specific changes in proteins that are the targets in targeted therapy,” Wohlgemuth explains. “If I know there is a gene that would be targeted with targeted therapy but it’s not being expressed at all, it’s been wiped out genetically, then in almost all cases that therapy will be ineffective in treating that tumor.”
The new service has generated a “massive response,” Wohlgemuth adds, signaling a major uptick in interest and engagement around cancer genomics.
The global next-generation sequencing market will hit $14 billion by 2024, fueled by efforts to develop companion diagnostics and biomarkers for use in cancer treatments, according to a recent report by Grand View Research. In addition, the substantial decline in the cost of the technology and the introduction of novel platforms and whole genome sequencers will expand access and market penetration, the report says.
What is genome sequencing?
Genomic sequencing is determining the order of DNA nucleotides — adenine, guanine, thymine and cytosine — in a genome. An individual’s genome contains more than 3 billion of these genetic fingerprints. Decoding a genome is typically done by high-tech equipment that scans the genome and spits out a sequence of As, Gs, Ts and Cs.
A DNA sequencing reaction yields a sequence that is several hundred letters long, according to genome.gov. A typical sequence can run for thousands of letters.
Once the genome has been decoded, bioinformatics stores and analyzes the data. Scientists share the sequences through databases to where they can help to inform understanding of diseases and the usefulness of potential therapies.
Technology is evolving
During the last five to ten years, genomic sequencing technology has evolved to where DNA can be sequenced at scale and in a deep way that looks for mutations that may be expressed at low levels.
“We’re able to go deep," says Wohlgemuth. "We’re able to go wide. We can now assess maybe 400 or 500 genes or the whole genome in one reaction. That’s really made it possible to generate all the data across all the relevant genes in cancer at a depth that makes it sensitive enough.”
Coupled with this has been advances in bioinformatics that allow scientists to take that huge dataset and reduce it to an actionable report, he adds.
But while cancer genomics and noninvasive prenatal testing are on solid ground vis à vis clinical validation, other fields are not as reliable when it comes to interpreting the medical advice that is given. Areas like nutrition and performance are not nearly as far along as cancer in understanding what those results mean and what interventions an individual should take based on them.
In 2013, the Food and Drug Administration warned direct-to-consumer genomics company 23andMe that it needed regulatory approval to market its Personal Genome Service. “We still do not have nay assurance that the firm has analytically or clinically validated the PGS for its intended uses,” the letter stated.
For cancer genomics and other fields where genomics is more advanced, the biggest challenge to expanding access has been the complexity of the process — finding a way to sort through hundreds of genes and reams of literature and come up with a positive treatment plan.
“The inability to deliver that simplicity has been a huge barrier in the past because the last thing the oncologist wants is a gigantic pile of genomic information that they can’t really act on and they have their patient asking lots of questions,” Wohlgemuth says.
Other barriers include getting an oncologist, pathologist and hospital to cooperate in sending a tissue sample to the testing laboratory. Until there’s adequate reimbursement, it won’t be possible to offer genomic sequencing and tumor analysis to large populations. While Medicare and major health plans reimburse at some level for genomic testing, “it’s not up to speed with the science,” Wohlgemuth says.
In the hope of boosting coverage, the Personalized Medicine Coalition is funding a heath economic analysis of the benefit of tumor genetic testing. The Fred Hutchison Cancer Center will conduct the analysis and the results expected to be released next year.