TY - JOUR AB - Cancer arises from a multi‑step cellular transformation process where some mutations may be inherited, while others are acquired during the process of malignant transformation. Aberrations in the BCL2 associated transcription factor 1 (BCLAF1) gene have previously been identified in patients with cancer and the aim of the present study was to identify structural variants (SVs) and the effects of BCLAF1 gene silencing on cell transformation. Whole‑genome sequencing was performed on DNA isolated from tumour biopsies with a histologically confirmed diagnosis of oesophageal squamous cell carcinoma (OSCC). Paired‑end sequencing was performed on the Illumina HiSeq2000, with 300 bp reads. Reads were aligned to the Homo sapiens reference genome (NCBI37) using ELAND and CASAVA software. SVs reported from the alignment were collated with gene loci, using the variant effect predictor of Ensembl. The affected genes were subsequently cross‑checked against the Genetic Association Database for disease and cancer associations. BCLAF1 deletion was identified as a noteworthy SV that could be associated with OSCC. Transient small interfering RNA‑mediated knockdown of BCLAF1 resulted in the altered expression of several downstream genes, including downregulation of the proapoptotic genes Caspase‑3 and BAX and the DNA damage repair genes exonuclease 1, ATR‑interacting protein and transcription regulator protein BACH1. BCLAF1 deficiency also attenuated P53 gene expression. Inhibition of BCLAF1 expression also resulted in increased colony formation. These results provide evidence that the abrogation of BCLAF1 expression results in the dysregulation of several cancer signalling pathways and abnormal cell proliferation. AD - Department of Integrative Biomedical Sciences, Division of Medical Biochemistry and Structural Biology, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, Western Cape 7925, South Africa AU - Mwapagha,Lamech,M. AU - Chibanga,Vimbaishe AU - Shipanga,Hendrina AU - Parker,M.,Iqbal DA - 2021/10/01 DO - 10.3892/or.2021.8180 IS - 4 JO - Oncol Rep KW - tumour mutations BCL2 associated transcription factor 1 deletion insertions and deletions Whole Genome Sequencing PY - 2021 SN - 1021-335X 1791-2431 SP - 229 ST - New insights from Whole Genome Sequencing: BCLAF1 deletion as a structural variant that predisposes cells towards cellular transformation T2 - Oncology Reports TI - New insights from Whole Genome Sequencing: BCLAF1 deletion as a structural variant that predisposes cells towards cellular transformation UR - https://doi.org/10.3892/or.2021.8180 VL - 46 ER -