Simplified molecular classification of lung adenocarcinomas based on EGFR, KRAS, and TP53 mutations
Abstract Background 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 exclu...
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| Online Access: | https://doi.org/10.1186/s12885-020-6579-z |
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doaj-42cefdfcb2d246fca49bdc40bb0944202021-01-31T16:38:28ZengBMCBMC Cancer1471-24072020-01-0120111110.1186/s12885-020-6579-zSimplified molecular classification of lung adenocarcinomas based on EGFR, KRAS, and TP53 mutationsRoberto Ruiz-Cordero0Junsheng Ma1Abha Khanna2Genevieve Lyons3Waree Rinsurongkawong4Roland Bassett5Ming Guo6Mark J. Routbort7Jianjun Zhang8Ferdinandos Skoulidis9John Heymach10Emily B. Roarty11Zhenya Tang12L. Jeffrey Medeiros13Keyur P. Patel14Rajyalakshmi Luthra15Sinchita Roy-Chowdhuri16Department of Pathology, University of California San FranciscoDepartment of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer CenterDepartment of Hematopathology, The University of Texas MD Anderson Cancer CenterDepartment of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer CenterDepartment of Biostatistics, The University of Texas MD Anderson Cancer CenterDepartment of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer CenterDepartment of Hematopathology, The University of Texas MD Anderson Cancer CenterDepartment of Pathology, The University of Texas MD Anderson Cancer CenterDepartment of Biostatistics, The University of Texas MD Anderson Cancer CenterDepartment of Biostatistics, The University of Texas MD Anderson Cancer CenterDepartment of Biostatistics, The University of Texas MD Anderson Cancer CenterDepartment of Biostatistics, The University of Texas MD Anderson Cancer CenterDepartment of Pathology, The University of Texas MD Anderson Cancer CenterDepartment of Pathology, The University of Texas MD Anderson Cancer CenterDepartment of Pathology, The University of Texas MD Anderson Cancer CenterDepartment of Pathology, The University of Texas MD Anderson Cancer CenterDepartment of Hematopathology, The University of Texas MD Anderson Cancer CenterAbstract Background 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 seven 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 co-mutations 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 seven 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.https://doi.org/10.1186/s12885-020-6579-zLung adenocarcinomaNext generation sequencingMolecular subtypes |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
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 |
| spellingShingle |
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 Simplified molecular classification of lung adenocarcinomas based on EGFR, KRAS, and TP53 mutations BMC Cancer Lung adenocarcinoma Next generation sequencing Molecular subtypes |
| author_facet |
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 |
| author_sort |
Roberto Ruiz-Cordero |
| title |
Simplified molecular classification of lung adenocarcinomas based on EGFR, KRAS, and TP53 mutations |
| title_short |
Simplified molecular classification of lung adenocarcinomas based on EGFR, KRAS, and TP53 mutations |
| title_full |
Simplified molecular classification of lung adenocarcinomas based on EGFR, KRAS, and TP53 mutations |
| title_fullStr |
Simplified molecular classification of lung adenocarcinomas based on EGFR, KRAS, and TP53 mutations |
| title_full_unstemmed |
Simplified molecular classification of lung adenocarcinomas based on EGFR, KRAS, and TP53 mutations |
| title_sort |
simplified molecular classification of lung adenocarcinomas based on egfr, kras, and tp53 mutations |
| publisher |
BMC |
| series |
BMC Cancer |
| issn |
1471-2407 |
| publishDate |
2020-01-01 |
| description |
Abstract Background 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 seven 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 co-mutations 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 seven 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. |
| topic |
Lung adenocarcinoma Next generation sequencing Molecular subtypes |
| url |
https://doi.org/10.1186/s12885-020-6579-z |
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