ECE2022 Eposter Presentations Endocrine-Related Cancer (61 abstracts)
Genes involved in chromatin-remodeling complex could alter the regulation of alternative splicing in lungNENs
Antonio Agraz-Doblas 1,2,3 , Ricardo Blázquez-Encinas 1,2,3 , Víctor García Vioque 1,2,3 , Nicolás Alcalá 4 , Alexandra Sexton 4 , María Trinidad Moreno Montilla 1,2,3 , Emilia Alors-Perez 1,2,3 , pilar salamanca jimenez 1,2,3 , Matthieu Foll 4 , Lynnette Ferná nez Cuesta 4 , Alejandro Ibañez Costa 1,2,3 & Justo P. Castaño 1,2,3,5
1Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), Córdoba, Spain; 2Department of Cell Biology, Physiology and Immunology, University of Cordoba, Córdoba, Spain; 3Reina Sofia University Hospital, Córdoba, Spain; 4Rare Cancers Genomics Team, Genomics Epidemiology Brand, International Agency for Research on Cancer (IARC/WHO), Lyon, France; 5CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Spain
Lung neuroendocrine neoplasms (LungNENs) comprise a diverse group of rare tumors with a commonly difficult and late diagnosis, which often require complex management and treatment. The most frequently mutated genes in LungNENs have recently been identified, including known components of the chromatin-regulating pathways such as MEN1, PSIP1 and ARID1A, which are the subject of ongoing detailed studies. In contrast, other key regulatory mechanisms, particularly posttranscriptional processes linked to RNA regulation and downstream mechanisms involving RNA regulation, remain largely unexplored. Therefore, the main objective of this study was to gain further insight into the role of chromatin-remodeling genes in LungNENs by focusing not only on their mutations but also in their potential interactions with RNA biology. To this end, we used RNAseq data from two distinct cohorts, the first one included 20 lung atypical carcinoids (EGAS00001003699) and the second cohort included 30 typical and atypical carcinoids (SRP156394). To investigate the potential impact of dysregulation of the selected genes we used a biocomputational approach, which enabled to explore the putative connections between the altered genes and other factors contributing to RNA processing, splicing and maturation. Interestingly, initial results already indicated that patients harboring mutations in genes of the chromatin-remodeling pathway also displayed a dramatic dysregulation in the expression levels of these same genes. Furthermore, a detailed examination of the association between the altered genes and particular changes in functional and gene enrichment categories revealed that the chromatin-remodeling machinery could likely modulate transcriptional activity, hence affecting crucial peripheral regulatory systems. Interestingly, samples presenting mutations in chromatin-remodeling pathway genes also showed different patterns in splicing-related genes, which may suggest a dysfunctional RNA processing. Altogether, our study supports the use of biocomputational approaches to discover new alterations in and relationships among regulatory systems, which could lead to the discovery of new biomarkers and therapeutic tools in LungNENs. Ongoing efforts are aimed at using functional assays with LungNEN cell models to better delineate these biocomputational outcomes.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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