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Sang-Won Um 1 Article
Non-small Cell Lung Cancer with Concomitant EGFR, KRAS, and ALK Mutation: Clinicopathologic Features of 12 Cases
Taebum Lee, Boram Lee, Yoon-La Choi, Joungho Han, Myung-Ju Ahn, Sang-Won Um
J Pathol Transl Med. 2016;50(3):197-203.   Published online April 18, 2016
DOI: https://doi.org/10.4132/jptm.2016.03.09
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AbstractAbstract PDF
Background
Although epidermal growth factor receptor (EGFR), v-Ki-ras2 Kirsten rat sarcoma viral oncogene (KRAS), and anaplastic lymphoma kinase (ALK) mutations in non-small cell lung cancer (NSCLC) were thought to be mutually exclusive, some tumors harbor concomitant mutations. Discovering a driver mutation on the basis of morphologic features and therapeutic responses with mutation analysis can be used to understand pathogenesis and predict resistance in targeted therapy.
Methods
In 6,637 patients with NSCLC, 12 patients who had concomitant mutations were selected and clinicopathologic features were reviewed. Clinical characteristics included sex, age, smoking history, previous treatment, and targeted therapy with response and disease-free survival. Histologic features included dominant patterns, nuclear and cytoplasmic features.
Results
All patients were diagnosed with adenocarcinoma and had an EGFR mutation. Six patients had concomitant KRAS mutations and the other six had ALK mutations. Five of six EGFR-KRAS mutation patients showed papillary and acinar histologic patterns with hobnail cells. Three of six received EGFR tyrosine kinase inhibitor (TKI) and showed partial response for 7–29 months. All six EGFR-ALK mutation patients showed solid or cribriform patterns and three had signet ring cells. Five of six EGFR-ALK mutation patients received EGFR TKI and/or ALK inhibitor and four showed partial response or stable disease, except for one patient who had acquired an EGFR mutation.
Conclusions
EGFR and ALK mutations play an important role as driver mutations in double mutated NSCLC, and morphologic analysis can be used to predict treatment response.

Citations

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    Annals of Oncology.2022; 33(5): 466.     CrossRef
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    Cancers.2022; 14(14): 3323.     CrossRef
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    PLOS ONE.2022; 17(10): e0276161.     CrossRef
  • Potential Therapeutic Strategy for EGFR-Mutant Lung Cancer With Concomitant EML4-ALK Rearrangement—Combination of EGFR Tyrosine Kinase Inhibitors and ALK Inhibitors
    Ming-Hung Huang, Jih-Hsiang Lee, Pei-Shan Hung, James Chih-Hsin Yang
    JTO Clinical and Research Reports.2022; 3(11): 100405.     CrossRef
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    Diagnostics.2022; 12(11): 2644.     CrossRef
  • A single center analysis of first-line treatment in advanced KRAS mutant non-small cell lung cancer: real-world practice
    Yanxia Liu, Yuan Gao, Ying Wang, Cong Zhao, Zhiyun Zhang, Baolan Li, Tongmei Zhang
    BMC Cancer.2022;[Epub]     CrossRef
  • High frequency of KRAS and EGFR mutation profiles in BRAF-negative thyroid carcinomas in Indonesia
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    BMC Research Notes.2022;[Epub]     CrossRef
  • Targeted next-generation sequencing for cancer-associated gene mutation and copy number detection in 206 patients with non–small-cell lung cancer
    Songbai Zheng, Xiaodan Wang, Ying Fu, Beibei Li, Jianhua Xu, Haifang Wang, Zhen Huang, Hui Xu, Yurong Qiu, Yaozhou Shi, Kui Li
    Bioengineered.2021; 12(1): 791.     CrossRef
  • How mathematical modeling could contribute to the quantification of metastatic tumor burden under therapy: insights in immunotherapeutic treatment of non-small cell lung cancer
    Pirmin Schlicke, Christina Kuttler, Christian Schumann
    Theoretical Biology and Medical Modelling.2021;[Epub]     CrossRef
  • A case of concomitant EGFR/ALK alteration against a mutated EGFR background in early-stage lung adenocarcinoma
    Ki-Chang Lee, Jiwon Koh, Doo Hyun Chung, Yoon Kyung Jeon
    Journal of Pathology and Translational Medicine.2021; 55(2): 139.     CrossRef
  • Malfeasance of KRAS mutations in carcinogenesis
    Rupal Tripathi, Shrinidhi Nathany, Anurag Mehta, Ullas Batra, Sakshi Mattoo, Mansi Sharma
    Clinical and Experimental Medicine.2021; 21(3): 439.     CrossRef
  • Detection of Low-Frequency KRAS Mutations in cfDNA From EGFR-Mutated NSCLC Patients After First-Line EGFR Tyrosine Kinase Inhibitors
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    Frontiers in Oncology.2021;[Epub]     CrossRef
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    Journal of Molecular Pathology.2021; 2(2): 173.     CrossRef
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    OncoTargets and Therapy.2021; Volume 14: 4671.     CrossRef
  • Untangling the KRAS mutated lung cancer subsets and its therapeutic implications
    Kulshrestha Ritu, Pawan Kumar, Amit Singh, K. Nupur, Sonam Spalgias, Parul Mrigpuri, Rajkumar
    Molecular Biomedicine.2021;[Epub]     CrossRef
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    Biomarkers in Medicine.2020; 14(7): 587.     CrossRef
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    PLOS ONE.2020; 15(3): e0229712.     CrossRef
  • KRAS oncogene may be another target conquered in non‐small cell lung cancer ( NSCLC )
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    Thoracic Cancer.2020; 11(12): 3425.     CrossRef
  • Epidemiologic Features of NSCLC Gene Alterations in Hispanic Patients from Puerto Rico
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    Cancers.2020; 12(12): 3492.     CrossRef
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    Seminars in Cancer Biology.2019; 54: 14.     CrossRef
  • Epidermal growth factor receptor (EGFR), KRAS, and BRAF mutations in lung adenocarcinomas: A study from India
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    Archives of Pathology & Laboratory Medicine.2019; 143(2): 174.     CrossRef
  • A sequential Monte Carlo algorithm for inference of subclonal structure in cancer
    Oyetunji E. Ogundijo, Kaiyi Zhu, Xiaodong Wang, Dimitris Anastassiou, Xiang Li
    PLOS ONE.2019; 14(1): e0211213.     CrossRef
  • The Presence of Concomitant Mutations Affects the Activity of EGFR Tyrosine Kinase Inhibitors in EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC) Patients
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  • Concurrent Driver Gene Mutations as Negative Predictive Factors in Epidermal Growth Factor Receptor-Positive Non-Small Cell Lung Cancer
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    American Journal of Clinical Oncology.2019; 42(4): 337.     CrossRef
  • Clinical features and therapeutic options in non‐small cell lung cancer patients with concomitant mutations of EGFR , ALK , ROS1 , KRAS or
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  • Intrinsic resistance to EGFR-Tyrosine Kinase Inhibitors in EGFR-Mutant Non-Small Cell Lung Cancer: Differences and Similarities with Acquired Resistance
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  • Clinical outcome of treatment of metastatic non-small cell lung cancer in patients harboring uncommon EGFR mutation
    J. Chantharasamee, N. Poungvarin, P. Danchaivijitr, S. Techawatanawanna
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  • Deregulated lncRNA expression profile in the mouse lung adenocarcinomas with KRAS‐G12D mutation and P53 knockout
    Meiqin Zhang, Nan Jiang, Renjie Cui, Sichen Du, Huayuan Ou, Tinglan Chen, Runsheng Ge, Duan Ma, Jin Zhang
    Journal of Cellular and Molecular Medicine.2019; 23(10): 6978.     CrossRef
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    JCO Clinical Cancer Informatics.2019; (3): 1.     CrossRef
  • EGFR, KRAS, BRAF, ALK, and cMET genetic alterations in 1440 Sardinian patients with lung adenocarcinoma
    Maria Colombino, Panagiotis Paliogiannis, Antonio Cossu, Davide Adriano Santeufemia, Maria Cristina Sini, Milena Casula, Grazia Palomba, Antonella Manca, Marina Pisano, Valentina Doneddu, Giuseppe Palmieri
    BMC Pulmonary Medicine.2019;[Epub]     CrossRef
  • Concomitant Presence of EGFR and ALK Fusion Gene Mutation in Adenocarcinoma of Lung: A Case Report and Review of the Literature
    Nishitha Thumallapally, Hana Yu, Mohammad Farhan, Uroosa Ibrahim, Maricel Odiami
    Journal of Pharmacy Practice.2018; 31(2): 244.     CrossRef
  • Double Trouble: A Case Series on Concomitant Genetic Aberrations in NSCLC
    Nele Van Der Steen, Yves Mentens, Marc Ramael, Leticia G. Leon, Paul Germonpré, Jose Ferri, David R. Gandara, Elisa Giovannetti, Godefridus J. Peters, Patrick Pauwels, Christian Rolfo
    Clinical Lung Cancer.2018; 19(1): 35.     CrossRef
  • KRAS oncogene in non-small cell lung cancer: clinical perspectives on the treatment of an old target
    Marta Román, Iosune Baraibar, Inés López, Ernest Nadal, Christian Rolfo, Silvestre Vicent, Ignacio Gil-Bazo
    Molecular Cancer.2018;[Epub]     CrossRef
  • Pulmonary Adenocarcinoma, Harboring Both an EGFR Mutation and ALK Rearrangement, Presenting a Stable Disease to Erlotinib and a Partial Response to Alectinib
    Akira Yokoyama, Atsuhisa Tamura, Kazuko Miyakawa, Kei Kusaka, Masahiro Shimada, Takashi Hirose, Hirotoshi Matsui, Masashi Kitani, Akira Hebisawa, Ken Ohta
    Internal Medicine.2018; 57(16): 2377.     CrossRef
  • Long-term survival with erlotinib in advanced lung adenocarcinoma harboring synchronous EGFR G719S and KRAS G12C mutations
    Biagio Ricciuti, Sara Baglivo, Vienna Ludovini, Angelo Sidoni, Giulio Metro, Marta Brambilla, Annamaria Siggillino, Maria Sole Reda, Alberto Rebonato, Daniele Maiettini, Rita Chiari
    Lung Cancer.2018; 120: 70.     CrossRef
  • Concomitant driver mutations in advanced EGFR-mutated non-small-cell lung cancer and their impact on erlotinib treatment
    Jan Nyrop Jakobsen, Eric Santoni-Rugiu, Morten Grauslund, Linea Melchior, Jens Benn Sørensen
    Oncotarget.2018; 9(40): 26195.     CrossRef
  • Implications of KRAS mutations in acquired resistance to treatment in NSCLC
    Marzia Del Re, Eleonora Rofi, Giuliana Restante, Stefania Crucitta, Elena Arrigoni, Stefano Fogli, Massimo Di Maio, Iacopo Petrini, Romano Danesi
    Oncotarget.2018; 9(5): 6630.     CrossRef
  • Alk Immunohistochemistry is Highly Sensitive and Specific for the Detection of Alk Translocated Lung Adenocarcinomas: Lessons from An Audit of Lung Cancer Molecular Testing
    YC Kheng, K Walsh, L Williams, WA Wallace, DJ Harrison, A Oniscu
    Journal of the Royal College of Physicians of Edinburgh.2018; 48(1): 20.     CrossRef
  • Targeting KRAS mutated non-small cell lung cancer: A history of failures and a future of hope for a diverse entity
    Alexios Matikas, Dimitrios Mistriotis, Vasilios Georgoulias, Athanasios Kotsakis
    Critical Reviews in Oncology/Hematology.2017; 110: 1.     CrossRef
  • Clinical Outcome of ALK -Positive Non–Small Cell Lung Cancer (NSCLC) Patients with De Novo EGFR or KRAS Co-Mutations Receiving Tyrosine Kinase Inhibitors (TKIs)
    Sabine Schmid, Oliver Gautschi, Sacha Rothschild, Michael Mark, Patrizia Froesch, Dirk Klingbiel, Hermann Reichegger, Wolfram Jochum, Joachim Diebold, Martin Früh
    Journal of Thoracic Oncology.2017; 12(4): 681.     CrossRef
  • EGFR and KRAS molecular genotyping for pulmonary carcinomas: Feasibility of a simple and rapid technique implementable in any department of pathology
    Vincent Thomas De Montpréville, Maria-Rosa Ghigna, Ludovic Lacroix, Antoinette Lemoine, Benjamin Besse, Olaf Mercier, Élie Fadel, Peter Dorfmuller, Thierry Le Chevalier
    Pathology - Research and Practice.2017; 213(7): 793.     CrossRef
  • MET Exon 14 Skipping Mutations in Lung Adenocarcinoma: Clinicopathologic Implications and Prognostic Values
    Geun Dong Lee, Seung Eun Lee, Doo-Yi Oh, Dan-bi Yu, Hae Min Jeong, Jooseok Kim, Sungyoul Hong, Hun Soon Jung, Ensel Oh, Ji-Young Song, Mi-Sook Lee, Mingi Kim, Kyungsoo Jung, Jhingook Kim, Young Kee Shin, Yoon-La Choi, Hyeong Ryul Kim
    Journal of Thoracic Oncology.2017; 12(8): 1233.     CrossRef
  • Non-Small-Cell Lung Cancer (NSCLC) Harboring ALK Translocations: Clinical Characteristics and Management in a Real-Life Setting: a French Retrospective Analysis (GFPC 02–14 Study)
    Jean-Bernard Auliac, Isabelle Monnet, Catherine Dubos-Arvis, Anne Marie Chiappa, Nathalie Baize, Suzana Bota, Alain Vergnenegre, Helene Doubre, Chrystele Locher, Acya Bizieux, Gilles Robinet, Christos Chouaid
    Targeted Oncology.2017; 12(6): 833.     CrossRef
  • Concomitant EML4-ALK rearrangement and EGFR mutation in non-small cell lung cancer patients: a literature review of 100 cases
    Giuseppe Lo Russo, Martina Imbimbo, Giulia Corrao, Claudia Proto, Diego Signorelli, Milena Vitali, Monica Ganzinelli, Laura Botta, Nicoletta Zilembo, Filippo de Braud, Marina Chiara Garassino
    Oncotarget.2017; 8(35): 59889.     CrossRef
  • Management of non-small cell lung cancer in the era of personalized medicine
    Gaetano Rocco, Alessandro Morabito, Alessandra Leone, Paolo Muto, Francesco Fiore, Alfredo Budillon
    The International Journal of Biochemistry & Cell Biology.2016; 78: 173.     CrossRef
  • A long-term survivor of non-small-cell lung cancer harboring concomitant EGFR mutation and ALK translocation
    Fumio Imamura, Takako Inoue, Madoka Kimura, Kazumi Nishino, Toru Kumagai
    Respiratory Medicine Case Reports.2016; 19: 137.     CrossRef

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