@article{b389759c59834a70b23157171d0916b6,
title = "SMARCA4 mutations in KRAS-mutant lung adenocarcinoma: a multi-cohort analysis",
abstract = "KRAS is a key oncogenic driver in lung adenocarcinoma (LUAD). Chromatin-remodeling gene SMARCA4 is comutated with KRAS in LUAD; however, the impact of SMARCA4 mutations on clinical outcome has not been adequately established. This study sought to shed light on the clinical significance of SMARCA4 mutations in LUAD. The association of SMARCA4 mutations with survival outcomes was interrogated in four independent cohorts totaling 564 patients: KRAS-mutant patients with LUAD who received nonimmunotherapy treatment from (a) The Cancer Genome Atlas (TCGA) and (b) the MSK-IMPACT Clinical Sequencing (MSK-CT) cohorts; and KRAS-mutant patients with LUAD who received immune checkpoint inhibitor-based immunotherapy treatment from (c) the MSK-IMPACT (MSK-IO) and (d) the Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) immunotherapy cohorts. Of the patients receiving nonimmunotherapy treatment, in the TCGA cohort (n = 155), KRAS-mutant patients harboring SMARCA4 mutations (KS) showed poorer clinical outcome [P = 6e-04 for disease-free survival (DFS) and 0.031 for overall survival (OS), respectively], compared to KRAS-TP53 comutant (KP) and KRAS-only mutant (K) patients; in the MSK-CT cohort (n = 314), KS patients also exhibited shorter OS than KP (P = 0.03) or K (P = 0.022) patients. Of patients receiving immunotherapy, KS patients consistently exhibited the shortest progression-free survival (PFS; P = 0.0091) in the MSK-IO (n = 77), and the shortest PFS (P = 0.0026) and OS (P = 0.0014) in the WFBCCC (n = 18) cohorts, respectively. Therefore, mutations of SMARCA4 represent a genetic factor leading to adverse clinical outcome in lung adenocarcinoma treated by either nonimmunotherapy or immunotherapy.",
keywords = "KRAS, SMARCA4 mutation, immunotherapy, lung adenocarcinoma, nonimmunotherapy, prognostics biomarker",
author = "Liang Liu and Tamjeed Ahmed and Petty, {William J.} and Stefan Grant and Jimmy Ruiz and Lycan, {Thomas W.} and Umit Topaloglu and Chou, {Ping Chieh} and Miller, {Lance D.} and Hawkins, {Gregory A.} and Alexander-Miller, {Martha A.} and O{\textquoteright}Neill, {Stacey S.} and Powell, {Bayard L.} and D{\textquoteright}Agostino, {Ralph B.} and Munden, {Reginald F.} and Boris Pasche and Wei Zhang",
note = "Funding Information: Research reported in this publication was supported by the National Cancer Institute{\textquoteright}s Cancer Center Support Grant award number P30CA012197 issued to the WFBCCC, the R21CA253362 issued to WZ and LL, the Wake Forest Baptist Comprehensive Cancer Center (WFBCCC)‐Center for Integrative Medicine Joint Pilot to LL, and the Cancer Genetics and Metabolism Program PUSH Pilot Award from Comprehensive Cancer Center at Wake Forest Baptist Medical Center issued to LL. WZ is supported by the Hanes and Willis Professorship in Cancer. BP is supported by the Charles L. Spurr Professorship Fund. Additional support for LL and WZ were provided by a Fellowship to WZ from the National Foundation for Cancer Research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute. Funding Information: Research reported in this publication was supported by the National Cancer Institute?s Cancer Center Support Grant award number P30CA012197 issued to the WFBCCC, the R21CA253362 issued to WZ and LL, the Wake Forest Baptist Comprehensive Cancer Center (WFBCCC)-Center for Integrative Medicine Joint Pilot to LL, and the Cancer Genetics and Metabolism Program PUSH Pilot Award from Comprehensive Cancer Center at Wake Forest Baptist Medical Center issued to LL. WZ is supported by the Hanes and Willis Professorship in Cancer. BP is supported by the Charles L. Spurr Professorship Fund. Additional support for LL and WZ were provided by a Fellowship to WZ from the National Foundation for Cancer Research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute. We thank Dr. Matthew S. Hellman at the MSKCC for helpful discussion of the results especially in regard to the MSK-IO cohort. We also acknowledge the editorial assistance of Karen Klein, MA, in the Wake Forest Clinical and Translational Science Institute, and Dr. Mac Robinson at the WFBCCC. Publisher Copyright: {\textcopyright} 2020 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies",
year = "2021",
month = feb,
doi = "10.1002/1878-0261.12831",
language = "English (US)",
volume = "15",
pages = "462--472",
journal = "Molecular Oncology",
issn = "1574-7891",
publisher = "Elsevier",
number = "2",
}