Multi-omic alterations of the SWI/SNF complex define a clinical subgroup in lung adenocarcinoma

Paola Peinado; Alvaro Andrades; Marta Cuadros; Maria Isabel Rodriguez; Isabel F Coira; Daniel J Garcia; Maria S Benitez-Cantos; Carlos Cano; Eduardo Zarzuela; Javier Muñoz; Claudia Loidi; Monica Saiz; Pedro P Medina

doi:10.1186/s13148-022-01261-3

Multi-omic alterations of the SWI/SNF complex define a clinical subgroup in lung adenocarcinoma

Clin Epigenetics. 2022 Mar 17;14(1):42. doi: 10.1186/s13148-022-01261-3.

Authors

Paola Peinado^#^{1

2}, Alvaro Andrades^#^{1

2}, Marta Cuadros^#^{2

3

4}, Maria Isabel Rodriguez^#^{2

3

4}, Isabel F Coira^{5

6}, Daniel J Garcia^{2

4}, Maria S Benitez-Cantos^{2

4}, Carlos Cano⁷, Eduardo Zarzuela⁸, Javier Muñoz⁸, Claudia Loidi⁹, Monica Saiz⁹, Pedro P Medina^{10

11

12}

Affiliations

¹ Department of Biochemistry and Molecular Biology I, University of Granada, Campus Fuentenueva s/n, 18071, Granada, Spain.
² GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, Granada, Spain.
³ Health Research Institute of Granada (Ibs.Granada), Granada, Spain.
⁴ Department of Biochemistry and Molecular Biology III and Immunology, University of Granada, Granada, Spain.
⁵ School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland.
⁶ Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Geneva, Switzerland.
⁷ Department of Computer Science and Artificial Intelligence, University of Granada, Granada, Spain.
⁸ Proteomics Unit, Spanish National Cancer Research Center, CNIO. Proteored-ISCIII, Madrid, Spain.
⁹ Pathological Anatomy, Universitary Hospital Cruces, University of Pais Vasco, Gipuzkoa, Spain.
¹⁰ Department of Biochemistry and Molecular Biology I, University of Granada, Campus Fuentenueva s/n, 18071, Granada, Spain. pedromedina@ugr.es.
¹¹ GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, Granada, Spain. pedromedina@ugr.es.
¹² Health Research Institute of Granada (Ibs.Granada), Granada, Spain. pedromedina@ugr.es.

^# Contributed equally.

Abstract

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.

Keywords: Epigenetics; Lung adenocarcinoma; Lung cancer; Multi-omics; Prognosis; SWI/SNF complex.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma of Lung* / genetics
DNA Methylation
DNA-Binding Proteins / genetics
Humans
Lung Neoplasms* / genetics
Transcription Factors / genetics
Transcription Factors / metabolism

Substances

DNA-Binding Proteins
Transcription Factors

Abstract

Publication types

MeSH terms

Substances

Grants and funding