Diagnostic Molecular Pathology in an Era of Genomics and Translational Bioinformatics : Diagnostic Molecular Pathology

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00019606-200803000-00001EditorialDiagnostic Molecular PathologyDiagnostic Molecular Pathology© 2008 by Lippincott Williams & Wilkins.17March 2008 p 1-2Diagnostic Molecular Pathology in an Era of Genomics and Translational BioinformaticsEditorialFarkas, Daniel H. PhDCenter for Molecular Medicine, Grand Rapids, MIReprints: Daniel H. Farkas, PhD, Center for Molecular Medicine, 301 Michigan St, NE, Suite 580, Grand Rapids, MI 49503 (e-mail: [email protected]).The dynamic nature of molecular pathology manifests itself continually. In the early 1980s, the notion of performing a Southern blot (or Northern blot-?!) in a clinical laboratory was arguably at least oxymoronic and certainly impractical. Similarly, in the mid-1980s the contamination-prone polymerase chain reaction seemed destined to remain a research tool. In the early 1990s, when solid-matrix supported DNA arrays arrogantly borrowed the term “chip” from the computer industry, could we imagine the day when the computer industry equivalent of billions of transistors per chip would manifest itself as the entire genome on a chip? Indeed, the concept of the whole genome and its now-completed sequence have helped define a new field: genomics.The authors of the popular book, Freakonomics, have suggested that because economics is merely a set of tools, these tools can be applied to any field of human endeavor. The eclectic set of targets in Freakonomics illustrates the authors' points in entertaining yet instructive ways. I cannot replicate the humor of that book here but if one thinks back 20 years to 1988 would it not have been ludicrous, if not humorous, to imagine using molecular biology to ask and answer questions about breast cancer prognosis, predisposition to coagulopathy, and whether a nonsmall cell lung cancer patient should or should not be treated with (then yet to be developed) Iressa? Because molecular biology is also merely a set of tools, it has turned out not to be so surprising that molecular biology in the clinical laboratory, also known as, molecular diagnostics and/or molecular pathology, can be applied to any area of laboratory medicine. By extension, because laboratory medicine supports every field of clinical medicine, the wide reach of molecular diagnostics is manifest destiny.Depending on one's definition of the “beginning” of molecular diagnostics, we are somewhere in the beginning of the third decade of practice. Though we started with hemocentric diseases like leukemia and sickle cell anemia due to the easy accessibility of blood, the field has matured around the leadership of infectious disease diagnostics. We now have the experience and tools to bring to the fore solutions for the health scourges of 21st century western civilization, that is, the multigenic and systems-wide targets with the more conventional disease and condition names of obesity, diabetes, cancer, cardiovascular disease, and even the holy grail, aging. Scholarly efforts like the one in this issue of Diagnostic Molecular Pathology,1 signal neither a beginning nor an end to this endeavor. This is no “tipping point” in time. But when we see publications that include in the same title the terms, “optimization,” “routine clinical use,” and “formalin–fixed, paraffin-embedded tissues,” it is a clarion call to those of us in the field: our Newtonian processes of rigorous empiricism are ready to be combined with the maturing field of bioinformatics for some dramatic Darwinian leaps forward.Bioinformatics? Certainly. With only as many genes as numerous lower life forms, readers recognize that Homo sapiens makes highly elastic and overlapping use of its genome. To make preliminary observations that biologic pathways are convergent at the genomic level between diseases as divergent, from a clinical classification point of view, muscular dystrophy and myocardial infarction (A. Butte, personal communication) is to realize that what we call translational medicine will see its successes only when we apply translational bioinformatics for purposes of diagnostics and more importantly, magic bullet style, personalized therapeutics.Chevy Chase once deadpanned, “I was told there would be no math,” when portraying President Ford answering a question in a debate against then-Governor Carter in 1976. Three decades later, the same cannot be said about the future of molecular pathology; there will be math, the study of relationships, and the assessment of laboratory values (just another term for biomarker, per A. Butte, Stanford) and those laboratory values will increasingly include expression analysis of seemingly disparate genes. Analytic, storage, and interpretive methods developed for optimal transformation of genetic, genomic, and biologic data into laboratory diagnostics and personalized therapeutics; this is translational bioinformatics and molecular pathologists must embrace it if we are to move the field forward in the genomic era. Indeed NIH Director, Elias Zerhouni has opined, “[i]t is the responsibility of those of us involved in today's biomedical research enterprise to translate the remarkable scientific innovations we are witnessing into health gains for the nation…At no other time has the need for a robust, bidirectional information flow between basic and translational scientists been so necessary.” We, in molecular pathology, are in a unique and enviable position to mediate this bidirectional translation.Does this role “doom” molecular pathologists to esoterica while recentralization of high volume “bread and butter” tests move to core laboratories? By extension, does applying genomics to “the next big thing” leave us eternally fighting with payers over reimbursement, keep us ever on the fringes of the clinical laboratory, make permanent our need to justify our existence to hospital administrators looking for quick return on investment? Maybe. I would prefer to take the optimistic approach to answer these questions; as recentralization occurs, those involved in diagnostic molecular pathology, particularly those who embrace translational bioinformatics, will always be at the forefront of what is new in genomics. And what is new in genomics today is what is standard of practice in a decade. Challenging? Yes. Exciting? Certainly.Molecular pathologists, both those at the frontline of clinical genomic (no longer an oxymoron) research and those practicing where the rubber hits the road, diagnostics on patient specimens, will continue to lead, if we choose to, and be looked to by our clinical colleagues as the translators of the genomic revolution. I once read that the pathologist can be thought of as the doctor's doctor. Never has this been more true than it is today and will continue to be in the foreseeable decades of this genomic century.REFERENCE1. Lyons-Weiler M, Hagenkord J, Sciulli C, et al. Optimization of the Affymetrix GeneChip Mapping 10K 2.0 Assay for routine clinical use on formalin-fixed paraffin-embedded tissues. Diagn Mol Pathol. 2008;17:3–13.[Context Link][Full Text][CrossRef][Medline Link]00019606-200803000-0000100019606_2008_17_3_weiler_optimization_|00019606-200803000-00001#xpointer(id(citation_FROM_JRF_ID_d7e140_citationRF_FLOATING))|11065404||ovftdb|SL00019606200817311065404citation_FROM_JRF_ID_d7e140_citationRF_FLOATING[Full Text]00019606-200803000-0000200019606-200803000-0000100019606_2008_17_3_weiler_optimization_|00019606-200803000-00001#xpointer(id(citation_FROM_JRF_ID_d7e140_citationRF_FLOATING))|11065213||ovftdb|SL00019606200817311065213citation_FROM_JRF_ID_d7e140_citationRF_FLOATING[CrossRef]10.1097%2FPDM.0b013e31815aca3000019606-200803000-0000100019606_2008_17_3_weiler_optimization_|00019606-200803000-00001#xpointer(id(citation_FROM_JRF_ID_d7e140_citationRF_FLOATING))|11065405||ovftdb|SL00019606200817311065405citation_FROM_JRF_ID_d7e140_citationRF_FLOATING[Medline Link]18303412Diagnostic Molecular Pathology in an Era of Genomics and Translational BioinformaticsFarkas Daniel H. 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