Introduction to Molecular Diagnostic Testing in Dermatology and Dermatopathology

Abstract

The complete sequencing of the human genome has ushered in an era of medical advances that was previously unimaginable. Scientists are continually discovering novel genetic and epigenetic mechanisms that are associated with human disease states and therapeutic responses. The ability to determine the underlying defect(s) in single-gene (Mendelian) diseases, many of which are rare, has improved both diagnosis in symptomatic patients and risk prediction of future disease in asymptomatic individuals. Potential applications of genomic discoveries include: (1) development of carrier, screening and diagnostic tests for single-gene disorders; (2) evaluation of several genetic loci in an effort to construct disease susceptibility profiles for non-Mendelian diseases, based on multiple gene and/or gene--environment relationships; and (3) pharmacogenomic testing to predict drug--genome interactions [1]. It has been estimated that ∼5{\%} of the ∼25,000 genes in the human genome are of diagnostic significance; therefore, the potential exists to develop ∼1,500 gene-based tests [2]. With regard to dermatologic conditions, exciting research is emerging and new applications are now being incorporated into clinical practice. Molecular diagnostic tests are transforming laboratory medicine and patient care, and becoming indispensable for physicians involved in the management of skin diseases, including dermatologists and dermatopathologists. Nucleic acid-based testing is becoming a crucial diagnostic tool, not only in the setting of inherited disorders (i.e., genodermatoses), but also for a wide variety of cutaneous solid and hematopoietic tumors, inflammatory dermatoses, and infectious conditions. In view of the increasing numbers of molecular diagnostic articles published in the dermatology literature, and potential application of these methodologies in clinical practice, a basic knowledge of the principles of molecular diagnostics is now essential for the physician who specializes in the diagnosis and/or treatment of skin diseases. Figure 1.1 illustrates the integration of research and diagnostic strategies in the study of skin diseases.