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Literature DB >> 27022036

MET Exon 14 Skipping in Non-Small Cell Lung Cancer.

Rebecca S Heist¹, Hyo Sup Shim², Shalini Gingipally³, Mari Mino-Kenudson⁴, Long Le⁴, Justin F Gainor³, Zongli Zheng⁴, Martin Aryee⁴, Junfeng Xia⁵, Peilin Jia⁶, Hailing Jin⁷, Zhongming Zhao⁸, William Pao⁷, Jeffrey A Engelman³, A John Iafrate⁴.

Abstract

BACKGROUND: Non-small cell lung cancers (NSCLCs) harboring specific genetic alterations can be highly sensitive to targeted therapies.
MATERIALS AND METHODS: We performed a targeted rearrangement assay on 54 NSCLCs across all stages that were from patients who were never smokers and did not have driver mutations. Because MET exon 14 skipping was the most frequent alteration found, we surveyed the results for MET exon 14 skipping at Massachusetts General Hospital (MGH) since the inclusion of this alteration into our current molecular profiling panel.
RESULTS: In a cohort of 54 never-smokers with lung cancers that were wild-type for known driver mutations, MET exon 14 skipping was the most frequently recurring alteration, occurring in 10 cancers (19%). Clinical testing at MGH via our next-generation sequencing (NGS) and NGS-rearrangement panels showed an additional 16 cases of MET exon 14 skipping, for an overall estimated frequency of 5.6%. A clinical case of a patient with MET exon 14 skipping treated with the MET inhibitor crizotinib is also described.
CONCLUSION: MET exon 14 skipping is a targetable gene alteration found in NSCLC. Patients with these alterations may respond well to MET inhibition. IMPLICATIONS FOR PRACTICE: MET exon 14 skipping occurs with an approximately 5% frequency in NSCLC and is seen in both squamous and adenocarcinoma histology. Patients whose cancers have MET exon 14 skipping can respond well to MET inhibitors. Molecular testing for MET exon 14 skipping should be performed on all lung cancers because this is a targetable alteration. ©AlphaMed Press.

Entities: Chemical Disease Gene Species

Keywords: Lung cancer; MET exon 14 skipping; Targeted therapy

Mesh：

Substances：

Year: 2016 PMID： 27022036 PMCID： PMC4828128 DOI： 10.1634/theoncologist.2015-0510

Source DB: PubMed Journal: Oncologist ISSN： 1083-7159

27 in total

1. Implementing multiplexed genotyping of non-small-cell lung cancers into routine clinical practice.

Authors: L V Sequist; R S Heist; A T Shaw; P Fidias; R Rosovsky; J S Temel; I T Lennes; S Digumarthy; B A Waltman; E Bast; S Tammireddy; L Morrissey; A Muzikansky; S B Goldberg; J Gainor; C L Channick; J C Wain; H Gaissert; D M Donahue; A Muniappan; C Wright; H Willers; D J Mathisen; N C Choi; J Baselga; T J Lynch; L W Ellisen; M Mino-Kenudson; M Lanuti; D R Borger; A J Iafrate; J A Engelman; D Dias-Santagata
Journal: Ann Oncol Date: 2011-11-09 Impact factor: 32.976

2. Crizotinib in ROS1-rearranged non-small-cell lung cancer.

Authors: Alice T Shaw; Sai-Hong I Ou; Yung-Jue Bang; D Ross Camidge; Benjamin J Solomon; Ravi Salgia; Gregory J Riely; Marileila Varella-Garcia; Geoffrey I Shapiro; Daniel B Costa; Robert C Doebele; Long Phi Le; Zongli Zheng; Weiwei Tan; Patricia Stephenson; S Martin Shreeve; Lesley M Tye; James G Christensen; Keith D Wilner; Jeffrey W Clark; A John Iafrate
Journal: N Engl J Med Date: 2014-09-27 Impact factor: 91.245

3. MET-Mutated NSCLC with Major Response to Crizotinib.

Authors: Melody A Mendenhall; Jonathan W Goldman
Journal: J Thorac Oncol Date: 2015-05 Impact factor: 15.609

4. Activation of MET via diverse exon 14 splicing alterations occurs in multiple tumor types and confers clinical sensitivity to MET inhibitors.

Authors: Garrett M Frampton; Siraj M Ali; Mark Rosenzweig; Juliann Chmielecki; Xinyuan Lu; Todd M Bauer; Mikhail Akimov; Jose A Bufill; Carrie Lee; David Jentz; Rick Hoover; Sai-Hong Ignatius Ou; Ravi Salgia; Tim Brennan; Zachary R Chalmers; Savina Jaeger; Alan Huang; Julia A Elvin; Rachel Erlich; Alex Fichtenholtz; Kyle A Gowen; Joel Greenbowe; Adrienne Johnson; Depinder Khaira; Caitlin McMahon; Eric M Sanford; Steven Roels; Jared White; Joel Greshock; Robert Schlegel; Doron Lipson; Roman Yelensky; Deborah Morosini; Jeffrey S Ross; Eric Collisson; Malte Peters; Philip J Stephens; Vincent A Miller
Journal: Cancer Discov Date: 2015-05-13 Impact factor: 39.397

5. MET Mutation Associated with Responsiveness to Crizotinib.

Authors: Saiama N Waqar; Daniel Morgensztern; Jennifer Sehn
Journal: J Thorac Oncol Date: 2015-05 Impact factor: 15.609

6. Functional expression and mutations of c-Met and its therapeutic inhibition with SU11274 and small interfering RNA in non-small cell lung cancer.

Authors: Patrick C Ma; Ramasamy Jagadeeswaran; Simha Jagadeesh; Maria S Tretiakova; Vidya Nallasura; Edward A Fox; Mark Hansen; Erik Schaefer; Katsuhiko Naoki; Alan Lader; William Richards; David Sugarbaker; Aliya N Husain; James G Christensen; Ravi Salgia
Journal: Cancer Res Date: 2005-02-15 Impact factor: 12.701

7. EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib.

Authors: William Pao; Vincent Miller; Maureen Zakowski; Jennifer Doherty; Katerina Politi; Inderpal Sarkaria; Bhuvanesh Singh; Robert Heelan; Valerie Rusch; Lucinda Fulton; Elaine Mardis; Doris Kupfer; Richard Wilson; Mark Kris; Harold Varmus
Journal: Proc Natl Acad Sci U S A Date: 2004-08-25 Impact factor: 11.205

8. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy.

Authors: J Guillermo Paez; Pasi A Jänne; Jeffrey C Lee; Sean Tracy; Heidi Greulich; Stacey Gabriel; Paula Herman; Frederic J Kaye; Neal Lindeman; Titus J Boggon; Katsuhiko Naoki; Hidefumi Sasaki; Yoshitaka Fujii; Michael J Eck; William R Sellers; Bruce E Johnson; Matthew Meyerson
Journal: Science Date: 2004-04-29 Impact factor: 47.728

9. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib.

Authors: Thomas J Lynch; Daphne W Bell; Raffaella Sordella; Sarada Gurubhagavatula; Ross A Okimoto; Brian W Brannigan; Patricia L Harris; Sara M Haserlat; Jeffrey G Supko; Frank G Haluska; David N Louis; David C Christiani; Jeff Settleman; Daniel A Haber
Journal: N Engl J Med Date: 2004-04-29 Impact factor: 91.245

10. Activation of MET by gene amplification or by splice mutations deleting the juxtamembrane domain in primary resected lung cancers.

Authors: Ryoichi Onozato; Takayuki Kosaka; Hiroyuki Kuwano; Yoshitaka Sekido; Yasushi Yatabe; Tetsuya Mitsudomi
Journal: J Thorac Oncol Date: 2009-01 Impact factor: 15.609

28 in total

Review 1. MET exon 14 juxtamembrane splicing mutations: clinical and therapeutical perspectives for cancer therapy.

Authors: Sara Pilotto; Anastasios Gkountakos; Luisa Carbognin; Aldo Scarpa; Giampaolo Tortora; Emilio Bria
Journal: Ann Transl Med Date: 2017-01

2. Randomized phase 2 study of tivantinib plus erlotinib versus single-agent chemotherapy in previously treated KRAS mutant advanced non-small cell lung cancer.

Authors: David E Gerber; Mark A Socinski; Joel W Neal; Heather A Wakelee; Keisuke Shirai; Lecia V Sequist; Rachel P Rosovsky; Rogerio C Lilenbaum; Bruno R Bastos; Chao Huang; Melissa L Johnson; Paul J Hesketh; Deepa S Subramaniam; Martin F Dietrich; Feng Chai; Yunxia Wang; Julia Kazakin; Brian Schwartz; Joan H Schiller; Julie R Brahmer; Ronan J Kelly
Journal: Lung Cancer Date: 2018-02-03 Impact factor: 5.705

Review 3. Irreversible tyrosine kinase inhibition of epidermal growth factor receptor with afatinib in EGFR activating mutation-positive advanced non-small-cell lung cancer.

Authors: S Morin-Ben Abdallah; V Hirsh
Journal: Curr Oncol Date: 2018-06-13 Impact factor: 3.677

MET Exon 14 Skipping in Non-Small Cell Lung Cancer.

1. Implementing multiplexed genotyping of non-small-cell lung cancers into routine clinical practice.

2. Crizotinib in ROS1-rearranged non-small-cell lung cancer.

3. MET-Mutated NSCLC with Major Response to Crizotinib.

4. Activation of MET via diverse exon 14 splicing alterations occurs in multiple tumor types and confers clinical sensitivity to MET inhibitors.

5. MET Mutation Associated with Responsiveness to Crizotinib.

6. Functional expression and mutations of c-Met and its therapeutic inhibition with SU11274 and small interfering RNA in non-small cell lung cancer.

7. EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib.

8. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy.

9. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib.

10. Activation of MET by gene amplification or by splice mutations deleting the juxtamembrane domain in primary resected lung cancers.

Review 1. MET exon 14 juxtamembrane splicing mutations: clinical and therapeutical perspectives for cancer therapy.

2. Randomized phase 2 study of tivantinib plus erlotinib versus single-agent chemotherapy in previously treated KRAS mutant advanced non-small cell lung cancer.

Review 3. Irreversible tyrosine kinase inhibition of epidermal growth factor receptor with afatinib in EGFR activating mutation-positive advanced non-small-cell lung cancer.

4. Targeted Therapy Approaches for MET Abnormalities in Non-Small Cell Lung Cancer.

Review 5. MET in human cancer: germline and somatic mutations.

Review 6. A pharmacological exploration of targeted drug therapy in non-small cell lung cancer.

7. A lung adenocarcinoma patient with co-mutations of MET and EGFR exon20 insertion responded to crizotinib.

Review 8. The multiple paths towards MET receptor addiction in cancer.

9. Standardizing biomarker testing for Canadian patients with advanced lung cancer.

10. MET D1228N and D1246N are the Same Resistance Mutation in MET Exon 14 Skipping.