Authors' recommendations: Most tumours result from somatic DNA mutation events or, more rarely, from constitutional genetic abnormalities. In both cases, next-generation sequencing (NGS) technologies may contribute to a better understanding of tumorigenesis. The clinical validity and utility of molecular profiles obtained with these technologies form the subject of this assessment, in which these two aspects are centered on a theranostic approach and defined by the ACCE analytical framework. A few studies on the clinical validity and utility of NGS technologies were identified. They are one systematic review, two descriptive studies and a few narrative literature reviews, as well as some conference abstracts. The parameter deemed most important for assessing their clinical validity is the ability to sequence genes using archived or biopsy specimens or surgical resection pieces with demonstrated clinical relevance. In this regard, these studies show that NGS technologies are able to detect mutations associated with chemosensitivity or resistance to certain anticancer drugs. Here, certain analytical parameters, such as concordance and false positives, quantitatively support their clinical validity. Presently, the number of tumour mutations searched for to treat a given patient is limited in conventional clinical practice. Although high-throughput sequencing technologies are able to identify these mutations, their clinical utility, compared to that of the other gene-sequencing methods, is not apparent because of the required throughput. A rigorous efficiency analysis would be necessary before their clinical implementation. The experimental approach consists in searching for several targetable mutations by sequencing a large gene panel, the exome or the genome, and in treating the patient with a drug off-label or in a clinical trial. Since the number of potential mutations is large, an NGS technology, thanks to its high-throughput capacity, is useful. Presently, the results are fragmentary, and the reported clinical benefits have been modest. However, the preliminary results of ongoing studies are promising, and eventually, new data will guide the clinical management of tumours.

Project Status: Completed

Year Published: 2015

URL for published report: https://www.inesss.qc.ca/fileadmin/doc/INESSS/Rapports/Oncologie/INESSS_Sequencage_genetique.pdf

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: Canada

Organisation Name: Institut national d'excellence en sante et en services sociaux

Contact Address: L'Institut national d'excellence en sante et en services sociaux (INESSS) , 2021, avenue Union, bureau 10.083, Montreal, Quebec, Canada, H3A 2S9;Tel: 1+514-873-2563, Fax: 1+514-873-1369

Contact Name: demande@inesss.qc.ca

Contact Email: demande@inesss.qc.ca

Copyright: ©Gouvernement du Québec/Institut national d'excellence en santé et en services sociaux