MET Mutation Associated with Responsiveness to Crizotinib

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MET Mutation Associated with Responsiveness to Crizotinib Saiama N. Waqar, MD, Daniel Morgensztern, MD Journal of Thoracic Oncology Volume 10, Issue 5, Pages e29-e31 (May 2015) DOI: 10.1097/JTO.0000000000000478 Copyright © 2015 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 1 MET chr7:g.116412043G>C alteration as viewed in the Integrative Genomics Viewer (Broad Institute, Cambridge, MA). The guanine to cytosine alteration is highlighted at the terminus of MET exon 14. Journal of Thoracic Oncology 2015 10, e29-e31DOI: (10.1097/JTO.0000000000000478) Copyright © 2015 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 2 MET alteration and predicted outcomes. Each panel shows MET exon 14 and flanking DNA sequence with splicing events indicated by black lines followed by the resulting protein sequence. A, Normal MET sequence and splicing. The c-Cbl binding site (Y1021) is marked with a box. B, Effect of chr7:g.116412043G>C alteration (red, arrow) if splicing is unimpaired resulting in a p.D1028H substitution without deletion of exon 14. C, Alternately, as predicted by splice site algorithms, the variant could result in altered splicing with deletion of exon 14, as has been described for other MET splice site variants in lung cancer. Journal of Thoracic Oncology 2015 10, e29-e31DOI: (10.1097/JTO.0000000000000478) Copyright © 2015 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 3 Radiographic response to crizotinib. CT scans (A) at baseline and (B) after 6 weeks and (C) 6 months of crizotinib. CT, computed tomography. Journal of Thoracic Oncology 2015 10, e29-e31DOI: (10.1097/JTO.0000000000000478) Copyright © 2015 International Association for the Study of Lung Cancer Terms and Conditions