Analysis of SWI/SNF catalytic subunits mutations and drug sensitivity in colorectal cancer.


Session type:


Sarah EL-Zahab1
1University of Sussex



SWI/SNF (SWitch/Sucrose Non-fermentable) are ATP-dependent chromatin remodelling complexes that alter chromatin structure regulating genetic expression and various biological processes within cells. SWI/SNF complex subunits are frequently mutated in a wide range of human cancers (Shain and Pollack, 2013). This project explores the mutational frequencies and drug sensitivities of SWI/SNF complexes in colorectal carcinoma cell lines.(Forbes et al., 2015).


Colorectal cancer cell lines were identified by searching Catalogue of Somatic Mutations in Cancer(COSMIC). Data of co-mutation rates were collected from studies on database sets from John Hopkins University and Cancer Genome Atlas on colorectal cancer. Drug sensitivity for each of the colorectal cancer cell lines was derived from Drug Sensitivity Browser in COSMIC.


Detailed database search has revealed that approximately 44% of the colorectal cancer cell lines are associated with SWI/SNF mutations with high  co-mutation rates in both catalytic subunits (SMARCA2 & SMARCA4). SWI/SNF mutant colorectal cancer cell lines are more sensitive to anticancer therapy compared to non-SWI/SNF mutant cell lines. SNF2-N and Bromodomain are the 2 most highly mutated domains in both catalytic subunits.


The effect of high co-mutation rates in both catalytic subunits on survival of tumour cells is dependent on the functional specificity of SWI/SNF complex and the subsequent impact of its loss in different cell types. Moreover, the increased drug sensitivity of SWI/SNF compared to non-SWI/SNF mutant cell lines, is deduced to be related to the association of SWI/SNF complexes with DNA repair proteins. Inactivating mutations in the remodelling complex would result in the loss of the repair proteins, affecting the efficiency of DNA repair mechanisms making it more sensitive to anticancer therapy. Recent research revealed that SNF2-N and Bromodomain inhibitors are being considered as potential therapeutic targets in the treatment SMARCA4-mutant cancer cells due to their critical role maintaining SWI/SNF function (Vangamudi et al., 2015).