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Expert Rev Mol Diagn. 2011 Sep;11(7):703-9

Authors: Klee EW, Hoppman-Chaney NL, Ferber MJ

Abstract
During the last 25 years, a small number of meaningful DNA-based diagnostic tests have been available to aid in the diagnosis and subsequent treatment of heritable disorders. These tests have targeted a limited number of genes and are often ordered in serial testing strategies in which results from one preliminary test dictate the subsequent test orders. This approach can be both time and resource intensive when a patient requires several genes to be sequenced. Recently, there has been much discussion regarding how 'massively parallel' or 'next-generation' DNA sequencing will impact clinical care. While the technology promises to reduce the cost of sequencing an entire human genome to less than US$1000, one must question the diagnostic utility of complete genome sequencing for routine clinical testing, given the many interpretive challenges posed by this approach. At present, it appears next-generation DNA sequencing may provide the greatest benefit to routine clinical testing by enabling comprehensive multigene panel sequencing. This should provide an advantage over traditional Sanger-based sequencing strategies while limiting the total test output to sets to genes with known diagnostic value. This article will discuss the current and near future state of clinical testing approaches and explore what challenges must be addressed in order to extract diagnostic value from whole-exome sequencing and whole-genome sequencing, using hereditary colon cancer as an example.

PMID: 21902532 [PubMed - indexed for MEDLINE]

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