Quality Assurance in Molecular Genetic Testing Laboratories

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Abstract
Over the past decade many disease-causing or predisposing molecular changes in genes have been identified, permitting development of diagnostic tests. These analyses permit identification of affected persons, mutant gene carriers, and those at increased risk for developing selected disorders including single-gene defects and, recently, breast1,2 and colon3 cancer. Diagnostic tests with broader applications, such as assessing individual genetic response to pharmacologic agents,4,5 are expected to be available soon. However, concerns have been raised about performance of such testing. For example, it is widely accepted that integration of genetic testing into clinical practice requires preanalytical informed consent and preanalytical and postanalytical genetic counseling to prevent misuse of diagnostic results.6-8 Also, confidentiality policies must be developed to prevent genetic discrimination by insurers and others.6-9 Because molecular genetic testing frequently involves the use of reagents not approved by the Food and Drug Administration, is technical, and requires complex interpretation, it has been suggested that laboratories that offer such testing should be specifically regulated to ensure personnel standards and a high quality of testing. Currently, the Clinical Laboratory Improvement Amendments of 1988 (CLIA),10 mandates the regulation of clinical laboratories. They are based on a complexity model of testing with clinical molecular genetic analyses considered to be a high-complexity category. Although the high-complexity testing category includes 9 specialty quality assurance (QA) categories, a separate category for genetic testing does not exist. Recently, the National Institutes of Health–Department of Energy Task Force on Genetic Testing recommended that a specialty category of genetics be established for defining specific personnel standards for genetic testing and to monitor laboratory performance, including development of proficiency testing programs.6 However, members of the task force and others have cautioned that formulation of these regulations should not restrict access to testing.6,7 Thus, assessment of current clinical molecular genetic testing practices is important for rational development of public policy and regulatory requirements and to assess the impact of new regulations on QA and access, particularly for rare diseases.