@misc{10481/66378,
year = {2020},
month = {12},
url = {http://hdl.handle.net/10481/66378},
abstract = {Simple Summary: Mammalian SWI/SNF complexes regulate gene expression by reorganizing the
way DNA is packaged into chromatin. SWI/SNF subunits are recurrently altered in tumors at multiple
levels, including DNA mutations as well as alteration of the levels of RNA and protein. Cancer cell
lines are often used to study SWI/SNF function, but their patterns of SWI/SNF alterations can be
complex. Here, we present a comprehensive characterization of DNA mutations and RNA and protein
expression of SWI/SNF members in 38 lung adenocarcinoma (LUAD) cell lines. We show that over
85% of our cell lines harbored at least one alteration in one SWI/SNF subunit. In addition, over 75% of
our cell lines lacked expression of at least one SWI/SNF subunit at the protein level. Our catalog will
help researchers choose an appropriate cell line model to study SWI/SNF function in LUAD.
Abstract: Mammalian SWI/SNF (SWitch/Sucrose Non-Fermentable) complexes are ATP-dependent
chromatin remodelers whose subunits have emerged among the most frequently mutated genes
in cancer. Studying SWI/SNF function in cancer cell line models has unveiled vulnerabilities
in SWI/SNF-mutant tumors that can lead to the discovery of new therapeutic drugs. However,
choosing an appropriate cancer cell line model for SWI/SNF functional studies can be challenging
because SWI/SNF subunits are frequently altered in cancer by various mechanisms, including genetic
alterations and post-transcriptional mechanisms. In this work, we combined genomic, transcriptomic,
and proteomic approaches to study the mutational status and the expression levels of the SWI/SNF subunits in a panel of 38 lung adenocarcinoma (LUAD) cell lines. We found that the SWI/SNF
complex was mutated in more than 76% of our LUAD cell lines and there was a high variability in the
expression of the di erent SWI/SNF subunits. These results underline the importance of the SWI/SNF
complex as a tumor suppressor in LUAD and the di culties in defining altered and unaltered cell
models for the SWI/SNF complex. These findings will assist researchers in choosing the most suitable
cellular models for their studies of SWI/SNF to bring all of its potential to the development of novel
therapeutic applications.},
organization = {Ministry of Economy of Spain 	
SAF2015-67919-R},
organization = {Junta de Andalucía

CS2016-3
P12-BIO1655
PIGE-0440-2019
Pl-0245-2017
PI-0135-2020},
organization = {University of Granada 	
PPJIA2019-0
B-CTS-126-UGR18},
organization = {International Association for the Study of Lung Cancer (IASLC)},
organization = {Spanish Association for Cancer Research (LAB-AECC)},
organization = {PhD "La Caixa Foundation" 	
LCF/BQ/DE15/10360019},
organization = {"Fundacion Benefica Anticancer Santa Candida y San Francisco Javier" predoctoral fellowship},
organization = {European Commission

837897},
organization = {Spanish Ministry of Education, Culture and Sports FPU fellowship 	
FPU17/00067
FPU17/01258
FPU18/03709},
organization = {PhD FPI-fellowship 	
BES-2013-064596},
organization = {Fundación Científica de la Asociación Española Contra el Cáncer 	
GCB14-2170},
organization = {Fundación Ramon Areces},
organization = {Instituto de Salud Carlos III-Fondo de Investigación Sanitaria-Fondo Europeo de Desarrollo Regional `Una manera de hacer Europa' (FEDER) 	
PI19/00098},
publisher = {Mdpi},
keywords = {SWI/SNF complex},
keywords = {Lung cancer},
keywords = {Lung adenocarcinoma},
keywords = {Epigenetics},
keywords = {Cell model},
keywords = {Multi-omics},
title = {Comprehensive Analysis of SWI/SNF Inactivation in Lung Adenocarcinoma Cell Models},
doi = {10.3390/cancers12123712},
author = {Peinado, Paola and Andrades Delgado, Álvaro and Cuadros Celorrio, Marta Eugenia and Rodríguez Lara, María Isabel and García García, Daniel Jesús and Álvarez Pérez, Juan Carlos and Baliñas Gavira, Carlos and Arenas Molina, Alberto Manuel and Patiño Mercau, Juan Rodrigo and Sanjuan Hidalgo, Juan and Medina Vico, Pedro Pablo},
}