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Optimization of Routine Testing for MET Exon 14 Splice Site Mutations in NSCLC Patients
Clotilde Descarpentries, PharmD, Frédéric Leprêtre, PhD, Fabienne Escande, PharmD, PhD, Zoulika Kherrouche, PhD, Martin Figeac, PhD, Shéhérazade Sebda, MSc, Simon Baldacci, MD, PhD, Valérie Grégoire, Philippe Jamme, MD, Marie-Christine Copin, MD, PhD, David Tulasne, PhD, Alexis B. Cortot, MD, PhD Journal of Thoracic Oncology Volume 13, Issue 12, Pages (December 2018) DOI: /j.jtho Copyright © 2018 International Association for the Study of Lung Cancer Terms and Conditions
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Figure 1 Percentage of genomic alterations found in NSCLC patients according to different next-generation sequencing (NGS) panel assays. The pie charts show the percentages of main genomic alterations found by the targeted NGS panels (A) Colon1&Lung V2 on 1514 tumor samples and (B) CLAPv1 on 365 tumor samples. WT (wild-type) indicates the absence of any mutation in EGFR, KRAS, BRAF, ERBB2, and MET. Journal of Thoracic Oncology , DOI: ( /j.jtho ) Copyright © 2018 International Association for the Study of Lung Cancer Terms and Conditions
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Figure 2 Positions of the amplicons of targeted next-generation sequencing (NGS) panels and fragment analysis products below MET exon 14. Exon 14 of MET (140 bp located between genomic positions g and g on Homo sapiens chromosome 7, GRCh37, GenBank: CM or between cDNA positions c.2942 and c.3082 NM_ ) and its flanking intronic regions are represented, with its coverage by the single amplicon of the Colon&lung V2 panel and by the three amplicons of the CLAPv1 panel. Fragment analysis products covering 225 bp of the 5’ end and and 144 bp of the 3’ end of exon 14 are also shown. Journal of Thoracic Oncology , DOI: ( /j.jtho ) Copyright © 2018 International Association for the Study of Lung Cancer Terms and Conditions
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Figure 3 Percentage of tumors with MET exon 14 splice site mutations found in NSCLC patients by means of next-generation sequencing (NGS) panel assays and fragment analysis. (A) Percentage of tumor samples displaying MET exon 14 mutations as determined on 1514 NSCLC tumor samples by Colon&Lung V2 or fragment-length analysis. (B) Percentage of tumor samples displaying MET exon 14 mutations by CLAPv1 and fragment-length analysis combined, as determined on 365 NSCLC tumor samples. Journal of Thoracic Oncology , DOI: ( /j.jtho ) Copyright © 2018 International Association for the Study of Lung Cancer Terms and Conditions
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Figure 4 Molecular features of the 30 patients harboring somatic MET exon 14 alterations. Synthetic view of the MET exon 14 mutations detected (yellow squares) or not (grey squares) by the Colon&Lung V2 panel assay or by fragment-length analysis and CLAPv1 panel. Tumors examined by immunohistochemistry were each attributed one of four scores (0 to 3+) according to their level of MET expression. Score 0: no expression; score 3+ maximal expression. Samples displaying MET gene amplification (as determined by fluorescence in situ hybridization [FISH]) or an increased copy number (as determined by FISH or by counting reads from the NGS CLAPv1 panel) are indicated by red squares. ND, not determined. Journal of Thoracic Oncology , DOI: ( /j.jtho ) Copyright © 2018 International Association for the Study of Lung Cancer Terms and Conditions
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