Whole-Exome Sequencing of Bronchial Epithelial Cells Reveals a Genetic Print of Airway Remodelling in COPD.
Fiche publication
Date publication
juillet 2022
Journal
Biomedicines
Auteurs
Membres identifiés du Cancéropôle Est :
Pr POLETTE Myriam, Pr GERMAIN Adeline, Dr DORMOY Valerian
Tous les auteurs :
Germain A, Perotin JM, Delepine G, Polette M, Deslée G, Dormoy V
Lien Pubmed
Résumé
The remodelling of the airways is a hallmark of chronic obstructive pulmonary disease, but it is highly heterogeneous and erratically distributed in the airways. To assess the genetic print of remodelling in chronic obstructive pulmonary disease (COPD), we performed a comparative whole-exome sequencing analysis on microdissected bronchial epithelia. Lung resections from four non-COPD and three COPD subjects (ex-smokers and current smokers) were formalin-fixed paraffin-embedded (FFPE). Non-remodelled and remodelled bronchial epithelia were isolated by laser microdissection. Genomic DNA was captured and sequenced. The comparative quantitative analysis identified a list of 109 genes as having variants in remodelled epithelia and 160 genes as having copy number alterations in remodelled epithelia, mainly in COPD patients. The functional analysis highlighted cilia-associated processes. Therefore, bronchial-remodelled epithelia appeared genetically more altered than non-remodelled epithelia. Characterizing the unique molecular print of airway remodelling in respiratory diseases may help uncover additional factors contributing to epithelial dysfunctions, ultimately providing additional targetable proteins to correct epithelial remodelling and improve lung function.
Mots clés
COPD, airway epithelial cells, whole-exome sequencing
Référence
Biomedicines. 2022 07 15;10(7):