PT - JOURNAL ARTICLE AU - Roberto Ruiz-Cordero AU - Junsheng Ma AU - Abha Khanna AU - Genevieve Lyons AU - Waree Rinsurongkawong AU - Roland Bassett AU - Ming Guo AU - Mark J. Routbort AU - Jianjun Zhang AU - Ferdinandos Skoulidis AU - John Heymach AU - Emily B. Roarty AU - Zhenya Tang AU - L. Jeffrey Medeiros AU - Keyur P. Patel AU - Rajyalakshmi Luthra AU - Sinchita Roy Chowdhuri TI - Simplified Molecular Classification of Lung Adenocarcinomas Based on <em>EGFR</em>, <em>KRAS</em>, and <em>TP53</em> Mutations AID - 10.1101/525949 DP - 2019 Jan 01 TA - bioRxiv PG - 525949 4099 - http://biorxiv.org/content/early/2019/01/21/525949.short 4100 - http://biorxiv.org/content/early/2019/01/21/525949.full AB - 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.