The clinical laboratory’s journey towards accreditation in diagnostic genomics

Abstract

The sequencing of the human genome and the development of new genomic methods has resulted in an explosion in our understanding of the molecular basis of disease, and a consequent explosion in the complexity of molecular diagnostic tests. Clinical laboratories are naturally striving to implement molecular diagnostic tests based on genomic methods such as massively parallel sequencing in order to provide genetic diagnosis at the genome scale, while leveraging the parallel processing and nanoscale architecture inherent in these technologies to consolidate costs and maintain turnaround times. These very characteristics, however, challenge both laboratories and accrediting agencies, who must respectively provide and assess objective evidence of clinical utility, analytical performance and limitations for assays of exceeding analytical complexity. With reference to recent local and international guidelines, we will provide examples of the validation of massively parallel sequencing of targeted gene panels for the detection of germline and somatic sequence variation in the clinical cancer setting. Issues particular to the application of this technology to clinical testing, including the use of reference materials, the importance of bioin-formatic validation, and the problem of secondary findings, will be reviewed and discussed.