Clinical OMICs - Issue 7 - (Page 22)

Clinical OMICs SNAPSHOT The Value of Present and the Promise of Future Sequencing Strategies Richard Mazzarella, Ph.D. T 22 Clinical OMICs July 16, 2014 Russ London-Wikicommons he Human Genome Project provided a path for determining the genetic basis of many inherited diseases and neoplasms. So far, various efforts from both research institutions and private companies have yielded myriad single gene and disease panel tests for both cancer and various Mendelian diseases, which have proven quite useful in diagnosing and treating specific conditions. The scope of single gene tests is limited, making them less effective at identifying a patient's underlying disease state and appropriate cancer drug regimens. Large cancer panels containing all the actionable genes do better at elucidating this type of information. The maturation of next-generation sequencing (NGS) technology, though, has made whole-exome and whole-genome studies viable options, especially if they can be used to assemble a mineable knowledge base that could yield a more comprehensive understanding of disease. Currently, the cost of assessing mutations for a single gene is $300-$2,000/gene. Cancer mutation panels, the largest of which can include up to 250 genes, cost $2,000-$6,000/panel. In selecting whether to order tests, physicians must balance their emphasis and utility with economics: What information is important for diagnosis and treatment weighed against cost and what insurers will reimburse. Single gene tests, for instance, make the most sense when physicians suspect an inherited gene as predetermining a disorder, as with autosomal dominant or X-linked diseases such as Huntington's disease or Duchenne muscular dystrophy. Single gene tests can also be used to determine if particular genes exist that might increase a patient's susceptibility to disease, such as breast cancer. The first printout of the human genome as displayed at the Wellcome Collection, London Disease panels, on the other hand, can be extremely useful to verify the genetic cause of an inherited disease when clinical phenotypic evidence strongly suggests the syndrome or if the genetic risk to a familial disease has not been previously determined in a family member. But they also have limitations. The largest current cancer panel tests less than half of the genes currently associated with cancer in the COSMIC database, and a bit more than 1% of the genes in the entire human genome. In this context, a small panel seems woefully limited, as it targets only a specific cancer type (e.g., breast or lung) and restricts potential treatments to approved drugs for the cancer type based on known genes with well-characterized mutations in a particular tissue. Larger panels can provide more options, as they can identify mutations observed across cancer www.clinicalomics.com http://www.clinicalomics.com

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Clinical OMICs - Issue 7