AMA Publishing Group: Genetic Testing Topic Collection

Molecular Testing in Thyroid Cancer BRAF Mutation Status and Mortality Molecular Testing in Thyroid Cancer

Cappola AR, Mandel SJ. — Wed, 10 Apr 2013 00:00:00 GMT

Thyroid cancer is the ninth most common cancer in the United States, with an incidence that has been increasing sharply since the mid-1990s. The majority of thyroid cancers are papillary thyroid cancers (PTC), which arise from thyroid follicular cells. Papillary thyroid tumors grow slowly and often retain sufficient characteristics of thyroid follicular cells to take up iodine, allowing for treatment with radioiodine to ablate residual thyroid cancer cells in cases requiring additional therapy beyond surgery. Papillary thyroid cancer has an excellent prognosis, with 5-year survival rates of 98%. However, for the 7% of individuals with aggressive PTC, the natural history is unpredictable and additional therapeutic options are limited.

New Approaches to Molecular Diagnosis New Approaches to Molecular Diagnosis

Korf BR, Rehm HL. — Wed, 10 Apr 2013 00:00:00 GMT

Advances in understanding the molecular basis of rare and common disorders, as well as in the technology of DNA analysis, are rapidly changing the landscape of molecular genetic and genomic testing. High-resolution molecular cytogenetic analysis can now detect deletions or duplications of DNA of a few hundred thousand nucleotides, well below the resolution of the light microscope. Diagnostic testing for “single-gene” disorders can be done by targeted analysis for specific mutations, by sequencing a specific gene to scan for mutations, or by analyzing multiple genes in which mutation may lead to a similar phenotype. The advent of massively parallel next-generation sequencing facilitates the analysis of multiple genes and now is being used to sequence the coding regions of the genome (the exome) for clinical testing. Exome sequencing requires bioinformatic analysis of the thousands of variants that are identified to find one that is contributing to the pathology; there is also a possibility of incidental identification of other medically significant variants, which may complicate genetic counseling. DNA testing can also be used to identify variants that influence drug metabolism or interaction of a drug with its cellular target, allowing customization of choice of drug and dosage. Exome and genome sequencing are being applied to identify specific gene changes in cancer cells to guide therapy, to identify inherited cancer risk, and to estimate prognosis. Genomic testing may be used to identify risk factors for common disorders, although the clinical utility of such testing is unclear. Genetic and genomic tests may raise new ethical, legal, and social issues, some of which may be addressed by existing genetic nondiscrimination legislation, but which also must be addressed in the course of genetic counseling. The purpose of this article is to assist physicians in recognizing where new approaches to genetic and genomic testing may be applied clinically and in being aware of the principles of interpretation of test results.

The Indispensable Role of Professional Judgment in Genomic Medicine Professional Judgment in Genomic Medicine

McGuire AL, McCullough LB, Evans JP. — Wed, 10 Apr 2013 00:00:00 GMT

Whole-genome sequencing and whole-exome sequencing (WGS/WES) have become increasingly affordable and accessible to individuals. There are currently 3 main pathways through which a person can receive WGS/WES: as a research participant in a genomic study; through a direct-to-consumer personal genome company; or as part of clinical care. In the research context, the extent to which findings from WGS/WES are communicated to study participants and used to inform their clinical care is a topic of much debate, but guidelines suggest that investigators may have an obligation to offer at least some results to study participants.

Accessing Genomic Medicine Affordability, Diffusion, and Disparities Accessing Genomic Medicine

Tuckson RV, Newcomer L, De Sa JM. — Wed, 10 Apr 2013 00:00:00 GMT

Advances in the understanding of the genome, combined with affordable sequencing techniques and innovations in drug development, are ushering in an era of molecular diagnostics and individualized therapeutics with the potential to meaningfully enhance human health through effective prevention, diagnosis, and treatment. As the genetic origins of many diseases become better understood, risks and prognoses can be assessed based upon knowledge of genetic mutations, while biomarkers are becoming available to predict pharmacologic response in unique patients. This revolution in genomic medicine, sometimes also called personalized or precision medicine, has the ability to advance both disease prevention and patient outcomes.