2026-10-09T03:10:12Zhttps://riubu.ubu.es/oai/request

oai:riubu.ubu.es:10259/122422026-10-08T00:05:53Zcom_10259_6168com_10259_5086com_10259_2604col_10259_12236

SWI/SNF alterations in cancer: molecular targets and therapeutic implications Monteverde, Beatriz Moreno, Thaidy Fuente Vivas, Dalia de la Revilla, Carlos Casar, Berta Crespo, Piero Varela, Ignacio Cromatina Genética médica Chromatin Medical genetics Póster presentado en: 42 Congress SEBBM, Madrid, 16-19 july 2019 Background: SWI/SNF chromatin remodelling complex is altered in nearly 20% of all human tumor types, which places it as the most broadly mutated molecular system in human cancer, just after TP53 [1, 2]. Nevertheless, the molecular mechanisms through which these alterations foster cancer development remain to be fully understood. In addition, any potential susceptibility associated with SWI/SNF alterations might be exploited for the treatment of patients affected by different malignancies. Methodology: We have generated stably-transduced cell lines for a doxycycline-inducible vector that directs the expression of different shRNAs targeting ARID1A, ARID1B or ARID2 in different human cancer cell lines. We have studied the transcriptional alterations resulted from the deficiency of these subunits in different cellular contexts by RNA-Seq, as well as the changes in chromatin accessibility by ATAC-Seq. Additionally, we have studied the sensitivity of these cell lines to different antitumoral treatments. Results: We have identified molecular pathways differently expressed in the SWI/SNF-deficient cell lines that might explain some characteristics of the behaviour of these tumor cells. Thus, we have seen an overexpression of genes involved in ROS production, as well as genes encoding metallopeptidases, and a downregulation of genes related to cellular adhesion or tumor suppression. Finally, we have detected different sensitivities in the ARID-deficient cells to some treatments, like cis-platin, and PARP or EGFR inhibitors. 2026-10-07T10:37:01Z 2026-10-07T10:37:01Z 2019 info:eu-repo/semantics/conferenceObject info:eu-repo/semantics/acceptedVersion https://hdl.handle.net/10259/12242 eng info:eu-repo/semantics/openAccess application/pdf