Quality Control and Quality Assurance in Solid Tumor Molecular Genetic Testing

Abstract

During the past decade, a vast amount of knowledge has been gained regarding genes, gene products, and their role in human disease. This knowledge has allowed us to better understand many disease processes in terms of their molecular pathogenesis. Molecular diagnostics testing is a relatively recent specialty of laboratory medicine and is still in a state of flux on many levels, such as the choice of test, technology, automation, and reimbursement. Routine molecular diagnostics determinations of tumor specimens in the pathology laboratory have been performed since the late ‘90s, and these determinations have been mainly for classification of tumors, clonality determinations and tests such as microsatellite instability analysis to select patients for referral to clinical geneticists. Increasing number of targeted therapies have become available and enable treatment decisions based on the molecular features of the malignancy. Precision medicine has rapidly gained access to daily practice and for certain tumors, molecular tests have become at the corner stone of the treatment decision making. This has led to the development of new clinical molecular assays for use in diagnosis, prognosis, selection of therapeutic modalities, and monitoring of disease. The technologies that constitute molecular diagnostics such as first-generation amplification, deoxyribonucleic acid (DNA) probes, fluorescent in situ hybridization (FISH), second-generation such as biochips and microfluidics, next-generation sequencing, and biosensors are influencing the discovery of therapeutic molecules, the screening and diagnosis of patients, and the optimization of drug therapy. Whereas testing for inherited genetic diseases, cancer diagnosis, viral load, and infectious diseases continues to predominate, the impact of pharmacogenomics on molecular diagnostics is unknown. The operation of a clinical molecular pathology laboratory requires integration of expertise in medical, scientific, and clinical molecular pathology; resources, including facilities, equipment, and personnel; and skills in organization, administration, management, and communication.