Thursday, November 15, 2012

Using 'Good' Epigenetics To Combat 'Bad' Epigenetics

From our author K. John Morrow some disturbing news and also a sense of where may be in the future for epigenetics..  “There are two deeply disturbing properties of epigenetic inheritance that have been receiving much attention of late,” Morrow says.   “The first is the ability of certain classes of chemicals to cause epigenetic changes that can be transmitted transgenerationally. The second is the propensity of genetically stable tumor cells to display great epigenetic variation, driving their evolution and malignancy.”

Morrow, author of Kalorama’s Epigenetics market research report notes that.  Manikkam et al [PLOS ONE 7(9):e46249] report that Dioxin, a potent epimutagen, can induce multiple adult onset disease in the F3 generation when administered to gestating female rats. In another important study Ujvari and coworkers (Proc Biol Sci. 2012 Nov 7. [Epub ahead of print]) find that a bizarre transmissable facial cancer in the Tasmanian Devil, although genomically stable, undergoes extensive epigenetic changes that drive its tumorigenicity. Because of this variability the tumors evolves over time, and these changes can be transmitted to other animals through bodily contact. This rare marsupial has been pushed to the edge of extinction by this cancer.

"Connecting these two sets of observations, it seems highly possible that exposure of human populations to epimutagenic agents could induce rapidly evolving and extremely lethal cancers. Moreover, it is also possible that subsequent generations could inherit this genetic alteration."

Epigenetic investigations have focused largely on use of therapies that target methylation site next to controller elements of various oncogenes, as described in a recent Kalorama report. There is a high probability that combining epigenetic drugs with conventional therapies could stop tumor growth and at the same time slow down the uncontrolled variability of cancer that enables it to outrun therapeutic intervention.

At the same time, there is a pressing need for studies that investigate the role of environmental epimutagens in driving disease in both animal and  human populations.    

Tuesday, November 13, 2012

Kalorama Identifies 5 Areas Next Gen Sequencing Will Impact Healthcare

The idea of a patient’s DNA being routinely tested by a next-generation sequencer to help a doctor make a diagnosis may seem a bit futuristic right now.  We suggest that sequencers are expected to see usage in at least five clinical areas over the next several years.   At the same time, we warn, there are unpredictable variables which will affect the timing for each clinical application, including science, regulation and economics, not to mention the strengths and weaknesses of different sequencing technologies.

 Kalorama recently released a white paper titled "Next-Generation Sequencing Moves Into Clinical Applications" covering some of these perspectives, following the third edition of its full market research report on this industry, DNA Sequencing Equipment and Services Markets.

"There are several clinical areas where next-generation sequencers are likely to see rapid growth, causing the overall segment to become a large fraction of the sequencer market within five years," said Justin Saeks, Kalorama analyst and author of the report.  

According to Kalorama Information, these areas include:
  • ·         cancer diagnostics and treatment
  • ·         HLA/ MHC typing
  • ·         neonatal and prenatal testing
  • ·         pathogen detection
  • ·         pharmacogenetics.

Kalorama notes these areas are progressing gradually, due to the regulatory process, the complexity of the science, and the medical community's cautious approach with new tests.  Eventually, the technology is expected to gain significant momentum in healthcare, possibly more rapidly in Europe's easier regulatory environment, as the complex issues are addressed and the individual systems become proven in their applications.  

Kalorama suggests that different areas can have different requirements in terms of read length, accuracy, coverage, throughput, run time, sample size and other features, which may result in niches. For example, cancer applications might have specific needs for higher accuracy/ coverage, longer read length, and/ or single cell capability due to the large variety of cancers, the large genetic aberrations, and the heterogeneity of the tissue often involved, respectively. Over time, medical discoveries a long with technological advances in hardware, software, and reagents will continue to change this landscape.

"The continuing drop in sequencer and consumables costs, along with increases in performance, are the primary drivers of adoption into new applications," Saeks said. "But the exponential drop in the cost of sequencing may slow the revenue growth in the near term, as the complex factors affecting adoption will likely take some time to shake out."

A range of new challenges and questions are also likely to manifest in unforeseen ways, for example, relating to ethical, legal, and social aspects. Along with the scientific challenges, these may take ten years or more to address before a tipping point is reached. But in the long term, sequencers are eventually expected to become ubiquitous in healthcare, with patients having the DNA in their circulating blood tested regularly. In the meantime, instrument suppliers, diagnostics companies, and clinical labs will need to consider how the various trends will impact these applications in the rapidly changing market.

Kalorama Information's report, DNA Sequencing Equipment and Services Markets, 3rd Edition, contains a deeper discussion of some of these trends, a review of products currently on the market, and competitive positions of players. In addition to analyzing DNA sequencer sales and making forecasts for future sales, it also looks at sequencer consumables and services sales. The report can be found at