Optimization of Routine Testing for MET Exon 14 Splice Site Mutations in NSCLC Patients Clotilde Descarpentries, PharmD, Frédéric Leprêtre, PhD, Fabienne.

Slides:

Advertisements

Similar presentations

A Sensitive Method for Detecting EGFR Mutations in Non-small Cell Lung Cancer Samples with Few Tumor Cells Miguel A. Molina-Vila, PhD, Jordi Bertran-Alamillo,

Advertisements

Frances A Shepherd, MD, Rafael Rosell, MD Journal of Thoracic Oncology

Prognostic and Predictive Value of Epidermal Growth Factor Receptor Tyrosine Kinase Domain Mutation Status and Gene Copy Number for Adjuvant Chemotherapy.

Unique Genetic and Survival Characteristics of Invasive Mucinous Adenocarcinoma of the Lung Hyo Sup Shim, MD, PhD, Mari- Kenudson, MD, Zongli Zheng,

Epidermal Growth Factor Receptor-Related Tumor Markers and Clinical Outcomes with Erlotinib in Non-small Cell Lung Cancer: An Analysis of Patients from.

Molecular Diagnostic Profiling of Lung Cancer Specimens with a Semiconductor-Based Massive Parallel Sequencing Approach Volker Endris, Roland Penzel,

Receptor Tyrosine Kinase Fusions and BRAF Kinase Fusions are Rare but Actionable Resistance Mechanisms to EGFR Tyrosine Kinase Inhibitors Alexa B. Schrock,

EGFR-GRB2 Protein Colocalization Is a Prognostic Factor Unrelated to Overall EGFR Expression or EGFR Mutation in Lung Adenocarcinoma Maria I. Toki, MD,

EGFR Array: Uses in the Detection of Plasma EGFR Mutations in Non–Small Cell Lung Cancer Patients Irene Yam, BSc, David Chi-Leung Lam, MBBS, PhD, Kaimin.

High Incidence of Somatic BAP1 Alterations in Sporadic Malignant Mesothelioma Masaki Nasu, Mitsuru Emi, Sandra Pastorino, Mika Tanji, Amy Powers, Hugh.

Comprehensive Screening of Gene Copy Number Aberrations in Formalin-Fixed, Paraffin-Embedded Solid Tumors Using Molecular Inversion Probe–Based Single-

Detection of Rearrangements and Transcriptional Up-Regulation of ALK in FFPE Lung Cancer Specimens Using a Novel, Sensitive, Quantitative Reverse Transcription.

ERBB2-Mutated Metastatic Non–Small Cell Lung Cancer: Response and Resistance to Targeted Therapies Jody C. Chuang, MD, PhD, Henning Stehr, PhD, Ying.

T790M EGFR Mutation Detection in Cerebrospinal Fluid and Response to Osimertinib in a Lung Cancer Patient with Meningeal Carcinomatosis Hugo Gortais,

Volume 19, Issue 3, Pages (March 2017)

Suppression of Wild-Type Amplification by Selectivity Enhancing Agents in PCR Assays that Utilize SuperSelective Primers for the Detection of Rare Somatic.

Comprehensive Characterization of Oncogenic Drivers in Asian Lung Adenocarcinoma Shiyong Li, BS, Yoon-La Choi, MD, PhD, Zhuolin Gong, PhD, Xiao Liu, PhD,

SC17.02 Lung Cancer in China: Challenges and Perspectives

EGFR and HER2 Genomic Gain in Recurrent Non-small Cell Lung Cancer After Surgery: Impact on Outcome to Treatment with Gefitinib and Association with EGFR.

A Sensitive Method for Detecting EGFR Mutations in Non-small Cell Lung Cancer Samples with Few Tumor Cells Miguel A. Molina-Vila, PhD, Jordi Bertran-Alamillo,

Jessica J. Lin, MD, Lauren L. Ritterhouse, MD, PhD, Siraj M

Dramatic Response to Combination Erlotinib and Crizotinib in a Patient with Advanced, EGFR-Mutant Lung Cancer Harboring De Novo MET Amplification Justin.

Christopher R. Cabanski, Vincent Magrini, Malachi Griffith, Obi L

Characterization of Fibroblast Growth Factor Receptor 1 in Small-Cell Lung Cancer Anish Thomas, MD, Jih-Hsiang Lee, MD, Zied Abdullaev, PhD, Kang-Seo.

Detection of Discrepant Driver Mutations in a Patient with Two Synchronous Primary Non–Small Cell Lung Cancers (NSCLCs) with Liquid Biopsy Sotirios Lakis,

FISH Analysis of Crizotinib Target Genes ROS1/ALK/MET in Malignant Mesothelioma Sandra Salvi, PhD, Serena Varesano, PhD, Simona Boccardo, PhD, Jean Louis.

Durable Response to Tyrosine Kinase Inhibitor Therapy in a Lung Cancer Patient Harboring Epidermal Growth Factor Receptor Tandem Kinase Domain Duplication

MET Mutation Associated with Responsiveness to Crizotinib

Acquired BRAF V600E Mutation as Resistant Mechanism after Treatment with Third- Generation EGFR Tyrosine Kinase Inhibitor Alessandra Bearz, MD, Elisa.

T790M EGFR Mutation Detection in Cerebrospinal Fluid and Response to Osimertinib in a Lung Cancer Patient with Meningeal Carcinomatosis Hugo Gortais,

The Unique Characteristics of MET Exon 14 Mutation in Chinese Patients with NSCLC Si-Yang Liu, MD, Lan-Ying Gou, MD, An-Na Li, MD, Na-Na Lou, MMed, Hong-Fei.

Susan C. Scott, MD, Nathan A. Pennell, MD, PhD

Evaluation of Kras Gene Mutation and Copy Number in Thymic Carcinomas and Thymomas Hidefumi Sasaki, MD, PhD, Motoki Yano, MD, PhD, Yoshitaka Fujii, MD,

A Novel EGFRC797 Variant Detected in a Pleural Biopsy Specimen from an Osimertinib-Treated Patient Using a Comprehensive Hybrid Capture–Based Next- Generation.

Clinical Impact of Hybrid Capture–Based Next-Generation Sequencing on Changes in Treatment Decisions in Lung Cancer Anna Belilovski Rozenblum, MD, Maya.

Clinical Validation and Implementation of a Targeted Next-Generation Sequencing Assay to Detect Somatic Variants in Non-Small Cell Lung, Melanoma, and.

MET and EGFR Mutations Identified in ALK-Rearranged Pulmonary Adenocarcinoma: Molecular Analysis of 25 ALK-Positive Cases Jennifer M. Boland, MD, Jin.

Coexistence of the BRAF Mutation and EGFR Exon 20 Insertion in a Patient with Lung Adenocarcinoma Lih-Chyun Chang, MD, Kuan-Yu Chen, MD, PhD, Jin-Yuan.

Markus Rechsteiner, Adriana von Teichman, Jan H

Unique Genetic and Survival Characteristics of Invasive Mucinous Adenocarcinoma of the Lung Hyo Sup Shim, MD, PhD, Mari- Kenudson, MD, Zongli Zheng,

Combined Use of ALK Immunohistochemistry and FISH for Optimal Detection of ALK- Rearranged Lung Adenocarcinomas Lynette M. Sholl, MD, Stanislawa Weremowicz,

Volume 130, Issue 3, Pages (September 2013)

Kelsie L. Thu, BSc, Raj Chari, PhD, William W

PD-L1 Is Upregulated by Simultaneous Amplification of the PD-L1 and JAK2 Genes in Non–Small Cell Lung Cancer Seiichi Ikeda, MSc, Tatsuro Okamoto, MD,

Combinational Analysis of FISH and Immunohistochemistry Reveals Rare Genomic Events in ALK Fusion Patterns in NSCLC that Responds to Crizotinib Treatment

Generation and Sequencing of Pulmonary Carcinoid Tumor Cell Lines

Emergence of Preexisting MET Y1230C Mutation as a Resistance Mechanism to Crizotinib in NSCLC with MET Exon 14 Skipping Sai-Hong Ignatius Ou, MD, PhD,

Figure 1. Plasma next-generation sequencing (NGS) assay workflow, comparison of variant allelic fraction with ... Figure 1. Plasma next-generation sequencing.

Association between Congenital Lung Malformations and Lung Tumors in Children and Adults: A Systematic Review Arianna Casagrande, MD, Federica Pederiva,

Comparison of Four PD-L1 Immunohistochemical Assays in Lung Cancer

Molecular Analysis of Plasma From Patients With ROS1-Positive NSCLC

Jamie A. Saxon, PhD, Lynette M. Sholl, MD, Pasi A. Jänne, MD, PhD

High MET Gene Copy Number Leads to Shorter Survival in Patients with Non-small Cell Lung Cancer Heounjeong Go, MD, Yoon Kyung Jeon, MD, PhD, Hyo Jin.

Response to Crizotinib Observed in Lung Adenocarcinoma with MET Copy Number Gain but without a High-Level MET/CEP7 Ratio, MET Overexpression, or Exon.

Erratum Journal of Thoracic Oncology

Lung Adenocarcinomas with HER2-Activating Mutations Are Associated with Distinct Clinical Features and HER2/EGFR Copy Number Gains Chenguang Li, MD,

EGFR Mutations Detected in Plasma Are Associated with Patient Outcomes in Erlotinib Plus Docetaxel-Treated Non-small Cell Lung Cancer Philip C. Mack,

Daniel B. Costa, MD, PhD, Susumu Kobayashi, MD, PhD

Trends in Stage Distribution for Patients with Non-small Cell Lung Cancer: A National Cancer Database Survey Daniel Morgensztern, MD, Shean Huey Ng,

Impact of HER2 Gene and Protein Status on the Treatment Outcome of Cisplatin-Based Chemoradiotherapy for Locally Advanced Non-small Cell Lung Cancer

PTEN and PIK3CA Expression Is Associated with Prolonged Survival after Gefitinib Treatment in EGFR-Mutated Lung Cancer Patients Hideki Endoh, MD, PhD,

Compound Uncommon EGFR Mutations in a Patient with Advanced NSCLC and Durable Response to Sequential EGFR Targeted Therapies Mary Linton B Peters, MD,

Ernest Nadal, MD, Guoan Chen, MD, PhD, John R

Concomitant Epidermal Growth Factor Receptor Mutation and EML4-ALK Fusion in a Patient with Multifocal Lung Adenocarcinomas Jun Fan, MD Journal of Thoracic.

Clinical Implications of Variant ALK FISH Rearrangement Patterns

Activation of MET by Gene Amplification or by Splice Mutations Deleting the Juxtamembrane Domain in Primary Resected Lung Cancers Ryoichi Onozato, MD,

MET Exon 14 Alterations and New Resistance Mutations to Tyrosine Kinase Inhibitors: Risk of Inadequate Detection with Current Amplicon-Based NGS Panels

FGFR1 Amplification in Squamous Cell Carcinoma of The Lung

Waxing and Waning of MET Amplification in EGFR-Mutated NSCLC in Response to the Presence and Absence of Erlotinib Selection Pressure Joel P. Womack,

ALK Gene Rearrangements: A New Therapeutic Target in a Molecularly Defined Subset of Non-small Cell Lung Cancer Benjamin Solomon, MBBS, PhD, Marileila.

Presentation transcript:

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 1873-1883 (December 2018) DOI: 10.1016/j.jtho.2018.08.2023 Copyright © 2018 International Association for the Study of Lung Cancer Terms and Conditions

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 2018 13, 1873-1883DOI: (10.1016/j.jtho.2018.08.2023) Copyright © 2018 International Association for the Study of Lung Cancer Terms and Conditions

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.1164121902 and g.1164122042 on Homo sapiens chromosome 7, GRCh37, GenBank: CM000669.1 or between cDNA positions c.2942 and c.3082 NM_00127500.1) 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 2018 13, 1873-1883DOI: (10.1016/j.jtho.2018.08.2023) Copyright © 2018 International Association for the Study of Lung Cancer Terms and Conditions

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 2018 13, 1873-1883DOI: (10.1016/j.jtho.2018.08.2023) Copyright © 2018 International Association for the Study of Lung Cancer Terms and Conditions

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 2018 13, 1873-1883DOI: (10.1016/j.jtho.2018.08.2023) Copyright © 2018 International Association for the Study of Lung Cancer Terms and Conditions