Detection of MET Exon 14 Skipping Alterations in Lung Cancer Clinical Samples Using a PCR-Based Approach.

Autor: Sui JSY; Thoracic Oncology Research Group, Trinity Translational Medicine Institute, St. James's Hospital, Dublin, Ireland.; Department of Medical Oncology, Mater Misericordiae University Hospital, Dublin, Ireland., Finn SP; Thoracic Oncology Research Group, Trinity Translational Medicine Institute, St. James's Hospital, Dublin, Ireland.; Department of Histopathology, Cancer Molecular Diagnostics, Labmed Directorate, St. James's Hospital, Dublin, Ireland.; Department of Histopathology and Morbid Anatomy, Trinity College Dublin, Dublin, Ireland., Gray SG; Thoracic Oncology Research Group, Trinity Translational Medicine Institute, St. James's Hospital, Dublin, Ireland. sgray@stjames.ie.; Department of Clinical Medicine, Trinity College Dublin, Dublin, Ireland. sgray@stjames.ie.; School of Biological Sciences, Dublin Institute of Technology, Dublin, Ireland. sgray@stjames.ie.
Jazyk: angličtina
Zdroj: Methods in molecular biology (Clifton, N.J.) [Methods Mol Biol] 2021; Vol. 2279, pp. 145-155.
DOI: 10.1007/978-1-0716-1278-1_11
Abstrakt: The receptor tyrosine kinase (RTK) c-MET plays important roles in cancer, yet despite being frequently overexpressed, clinical responses to targeting this receptor have been limited in the clinical setting. A singular significant challenge has been the accurate identification of biomarkers for the selection of responsive patients. However, recently mutations which result in the loss of exon 14 (called METex14 skipping) have emerged as novel biomarkers in non-small cell lung carcinomas (NSCLC) to predict for responsiveness to targeted therapy with c-MET inhibitors. Currently, the diverse genomic alterations responsible for METex14 skipping pose a challenge for routine clinical diagnostic testing. Next generation sequencing (NGS) is the current gold standard for identifying the diverse mutations associated with METex14, but the cost for such a procedure remains to some degree prohibitive as often NGS is requested on a case-by-case basis, and many hospitals may not even have the capacity or resources to conduct NGS.However, PCR-based approaches to detect METex14 have been developed which can be conducted in most routine hospital laboratories and may therefore allow a cost-effective approach to pre-screen patients that may respond to c-MET inhibitors prior to conducting NGS, or until all patients will have NGS conducted as routine practise. In this chapter, we describe one such PCR-based approach for screening samples for the detection of METex14 in NSCLC.
Databáze: MEDLINE