Multi‑omic alterations of the SWI/SNF complex define a clinical subgroup in lung adenocarcinoma
Abstract
PPM's lab is funded by the Ministry of Economy of Spain (SAF2015-67919-R), Junta de Andalucia (P20-00688, PI-0135-2020, PIGE-0213-2020, PIGE-04402019, PI-0245-2017), University of Granada (B-CTS-480-UGR20), International Association for the Study of Lung Cancer (IASLC), and Spanish Association for Cancer Research (LAB-AECC-2018). PP is supported by a PhD "La Caixa Foundation"LCF/BQ/DE15/10360019 Fellowship. AA is supported by an FPU17/00067 fellowship. IFC was supported by a PhD FPI-fellowship (BES-2013-064596). DJG was supported by a "Fundacion Benefica Anticancer Santa Candida y San Francisco Javier"predoctoral fellowship. MSBC and CC's work is supported by the project DPI2017-84439-R Ministry of Economy of Spain and FEDER and by the fellowship "Beca de Iniciacion a la Investigacion del Plan Propio de Investigacion 2019" by University of Granada. MSBC is supported by an FPU19/00576 predoctoral fellowship. CNIO Proteomics Unit is a member of Proteored PRB3 and is supported by grant PT17/0019, of the PE I + D + i 2013-2016, funded by ISCIII and ERDF. ; SWI/SNF complexes are major targets of mutations in cancer. Here, we combined multiple "-omics" methods to assess SWI/SNF composition and aberrations in LUAD. Mutations in lung SWI/SNF subunits were highly recurrent in our LUAD cohort (41.4%), and over 70% of the mutations were predicted to have functional impact. Furthermore, SWI/ SNF expression in LUAD suffered an overall repression that could not be explained exclusively by genetic alterations. Finally, SWI/SNF mutations were associated with poorer overall survival in TCGA-LUAD. We propose SWI/SNF-mutant LUAD as a separate clinical subgroup with practical implications. ; Spanish Government SAF2015-67919-R DPI2017-84439-R ; Junta de Andalucia P20-00688 PI-0135-2020 PIGE-0213-2020 PIGE-0440-2019 PI-0245-2017 ; University of Granada B-CTS-480-UGR20 ; International Association for the Study of Lung Cancer (IASLC) ; Spanish Association for Cancer Research LAB-AECC-2018 ; La Caixa Foundation LCF/BQ/DE15/10360019 ; PhD FPI-fellowship BES-2013-064596 ; "Fundacion Benefica Anticancer Santa Candida y San Francisco Javier" predoctoral fellowship ; European Commission ; fellowship "Beca de Iniciacion a la Investigacion del Plan Propio de Investigacion 2019" by University of Granada Instituto de Salud Carlos III PT17/0019 ; European Commission PT17/0019 FPU17/00067 FPU19/00576
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