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Simplified Molecular Classification of Lung Adenocarcinomas Based on EGFR, KRAS, and TP53 Mutations

View ORCID ProfileRoberto Ruiz-Cordero, Junsheng Ma, Abha Khanna, Genevieve Lyons, Waree Rinsurongkawong, Roland Bassett, Ming Guo, Mark J. Routbort, Jianjun Zhang, Ferdinandos Skoulidis, John Heymach, Emily B. Roarty, Zhenya Tang, L. Jeffrey Medeiros, Keyur P. Patel, Rajyalakshmi Luthra, Sinchita Roy Chowdhuri
doi: https://doi.org/10.1101/525949
Roberto Ruiz-Cordero
1Department of Pathology, The University of California, San Francisco
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  • ORCID record for Roberto Ruiz-Cordero
  • For correspondence: Roberto.Ruiz-Cordero@ucsf.edu
Junsheng Ma
3Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
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Abha Khanna
4Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
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Genevieve Lyons
3Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
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Waree Rinsurongkawong
5Department of Thoracic/Head and Neck Medical Oncology; The University of Texas MD Anderson Cancer Center, Houston, TX, United States
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Roland Bassett
3Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
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Ming Guo
4Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
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Mark J. Routbort
2Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
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Jianjun Zhang
5Department of Thoracic/Head and Neck Medical Oncology; The University of Texas MD Anderson Cancer Center, Houston, TX, United States
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Ferdinandos Skoulidis
5Department of Thoracic/Head and Neck Medical Oncology; The University of Texas MD Anderson Cancer Center, Houston, TX, United States
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John Heymach
5Department of Thoracic/Head and Neck Medical Oncology; The University of Texas MD Anderson Cancer Center, Houston, TX, United States
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Emily B. Roarty
5Department of Thoracic/Head and Neck Medical Oncology; The University of Texas MD Anderson Cancer Center, Houston, TX, United States
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Zhenya Tang
2Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
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L. Jeffrey Medeiros
2Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
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Keyur P. Patel
2Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
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Rajyalakshmi Luthra
2Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
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Sinchita Roy Chowdhuri
4Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
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Abstract

Introduction Gene expression profiling has consistently identified three molecular subtypes of lung adenocarcinoma that have prognostic implications. To facilitate stratification of patients with this disease into similar molecular subtypes, we developed and validated a simple, mutually exclusive classification.

Methods Mutational status of EGFR, KRAS, and TP53 was used to define six mutually exclusive molecular subtypes. A development cohort of 283 cytology specimens of lung adenocarcinoma was used to evaluate the associations between the proposed classification and clinicopathologic variables including demographic characteristics, smoking history, fluorescence in situ hybridization and molecular results. For validation and prognostic assessment, 63 of the 283 cytology specimens with available survival data were combined with a separate cohort of 428 surgical pathology specimens of lung adenocarcinoma.

Results The proposed classification yielded significant associations between these molecular subtypes and clinical and prognostic features. We found better overall survival in patients who underwent surgery and had tumors enriched for EGFR mutations. Worse overall survival was associated with older age, stage IV disease, and tumors with comutations in KRAS and TP53. Interestingly, neither chemotherapy nor radiation therapy showed benefit to overall survival.

Conclusions The mutational status of EGFR, KRAS, and TP53 can be used to easily classify lung adenocarcinoma patients into six subtypes that show a relationship with prognosis, especially in patients who underwent surgery, and these subtypes are similar to classifications based on more complex genomic methods reported previously.

Footnotes

  • Disclaimers: The authors have nothing to disclose.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted January 21, 2019.
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Simplified Molecular Classification of Lung Adenocarcinomas Based on EGFR, KRAS, and TP53 Mutations
Roberto Ruiz-Cordero, Junsheng Ma, Abha Khanna, Genevieve Lyons, Waree Rinsurongkawong, Roland Bassett, Ming Guo, Mark J. Routbort, Jianjun Zhang, Ferdinandos Skoulidis, John Heymach, Emily B. Roarty, Zhenya Tang, L. Jeffrey Medeiros, Keyur P. Patel, Rajyalakshmi Luthra, Sinchita Roy Chowdhuri
bioRxiv 525949; doi: https://doi.org/10.1101/525949
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Simplified Molecular Classification of Lung Adenocarcinomas Based on EGFR, KRAS, and TP53 Mutations
Roberto Ruiz-Cordero, Junsheng Ma, Abha Khanna, Genevieve Lyons, Waree Rinsurongkawong, Roland Bassett, Ming Guo, Mark J. Routbort, Jianjun Zhang, Ferdinandos Skoulidis, John Heymach, Emily B. Roarty, Zhenya Tang, L. Jeffrey Medeiros, Keyur P. Patel, Rajyalakshmi Luthra, Sinchita Roy Chowdhuri
bioRxiv 525949; doi: https://doi.org/10.1101/525949

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