TY - JOUR
T1 - Implementation of next generation sequencing in clinical molecular diagnostic laboratories
T2 - advantages, challenges and potential
AU - Singh, Rajesh R.
AU - Luthra, Rajyalakshmi
AU - Routbort, Mark J.
AU - Patel, Keyur P.
AU - Medeiros, L. Jeffrey
N1 - Funding Information:
(available at www.wadsworth.org) and the United States Centers for Disease Control and Prevention. [27] Additionally, other agencies such as the American College of Medical Genetics,[28] Association for Molecular Pathology and CAP have proposed similar guidelines for the validation, testing and reporting of NGS results.[29,30] Several reports also have been published recently regarding the validation of NGS in clinical laboratories, and these reports provide a rich source of information regarding target capture technology, gene panels, sequencing platforms, reporting criteria and overall performance of the assays.[22,23,31–35] Other studies have performed one-on-one comparisons of sequencing platforms and have highlighted the advantages and drawbacks; these studies are helpful resources when one is trying to decide on an appropriate sequencing platform.[36– 39] Furthermore, in Europe, the EuroGenest project funded by the European Commission is an important entity involved in ensuring high quality of molecular testing. These efforts have been instrumental in establishing guidelines and approaches to ensure adequate validation and implementation of clinical molecular tests and guidelines for NGS testing (http://www. irdirc.org/guidelines-for-diagnostic-next-generation-sequencing, as accessed on 19 October 2015) have been published.[40] In a clinical molecular diagnostic laboratory, validation of mutation screening assays generally involves sequencing a set of tumors with known aberrations as detected by well-established techniques like Sanger sequencing and establishing the ability of the new assay to detect these mutations (analytical sensitivity, Table 2). This approach was fairly straightforward when low-or medium-throughput sequencing techniques were implemented. The massively parallel sequencing capabilities of NGS present a unique set of challenges of which the foremost is the selection of the sample set for validation. NGS assays involve simultaneous screening of tens to hundreds of genes. Ideally, adequate validation of the panel would require a set of validation tumor samples that collectively harbor mutations in every gene tested. This ideal approach is impractical.
Publisher Copyright:
© 2016 Taylor & Francis.
PY - 2016/1/2
Y1 - 2016/1/2
N2 - Next generation sequencing (NGS) technologies have the capacity to perform massively parallel sequencing of the genome. This capacity simultaneously facilitates sequencing large areas of the genome in multiple samples and has revolutionized clinical genomics, both for discovery and diagnostic screening of genomic aberrations. The implementation of these powerful technologies in a Clinical Laboratory Improvement Amendment certified and College of American Pathologists accredited clinical laboratory presents a unique challenge due to their complexity, volume and medico-legal implications of the data generated. Here, with a focus on routine clinical cancer diagnostics, we review recent progress in the implementation of NGS, associated recommendations and guidelines, and the advantages and challenges of implementing NGS. In the light of rapidly increasing acceptance of NGS to replace the classical first generation technologies in the clinical environment, we also discuss the potential of NGS to be the new ‘gold standard’ for genome sequencing and to further improve the implementation of precision medicine.
AB - Next generation sequencing (NGS) technologies have the capacity to perform massively parallel sequencing of the genome. This capacity simultaneously facilitates sequencing large areas of the genome in multiple samples and has revolutionized clinical genomics, both for discovery and diagnostic screening of genomic aberrations. The implementation of these powerful technologies in a Clinical Laboratory Improvement Amendment certified and College of American Pathologists accredited clinical laboratory presents a unique challenge due to their complexity, volume and medico-legal implications of the data generated. Here, with a focus on routine clinical cancer diagnostics, we review recent progress in the implementation of NGS, associated recommendations and guidelines, and the advantages and challenges of implementing NGS. In the light of rapidly increasing acceptance of NGS to replace the classical first generation technologies in the clinical environment, we also discuss the potential of NGS to be the new ‘gold standard’ for genome sequencing and to further improve the implementation of precision medicine.
KW - cancer genomics and diagnostics
KW - genome sequencing
KW - next generation sequencing
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U2 - 10.1080/23808993.2015.1120401
DO - 10.1080/23808993.2015.1120401
M3 - Review article
AN - SCOPUS:85012056177
SN - 2380-8993
VL - 1
SP - 109
EP - 120
JO - Expert Review of Precision Medicine and Drug Development
JF - Expert Review of Precision Medicine and Drug Development
IS - 1
ER -