New insights from Whole Genome Sequencing: BCLAF1 deletion as a structural variant that predisposes cells towards cellular transformation

  • Authors:
    • Lamech M. Mwapagha
    • Vimbaishe Chibanga
    • Hendrina Shipanga
    • M. Iqbal Parker
  • View Affiliations

  • Published online on: September 6, 2021     https://doi.org/10.3892/or.2021.8180
  • Article Number: 229
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

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.
View Figures
View References

Related Articles

Journal Cover

October-2021
Volume 46 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Mwapagha LM, Chibanga V, Shipanga H and Parker MI: New insights from Whole Genome Sequencing: BCLAF1 deletion as a structural variant that predisposes cells towards cellular transformation. Oncol Rep 46: 229, 2021
APA
Mwapagha, L.M., Chibanga, V., Shipanga, H., & Parker, M.I. (2021). New insights from Whole Genome Sequencing: BCLAF1 deletion as a structural variant that predisposes cells towards cellular transformation. Oncology Reports, 46, 229. https://doi.org/10.3892/or.2021.8180
MLA
Mwapagha, L. M., Chibanga, V., Shipanga, H., Parker, M. I."New insights from Whole Genome Sequencing: BCLAF1 deletion as a structural variant that predisposes cells towards cellular transformation". Oncology Reports 46.4 (2021): 229.
Chicago
Mwapagha, L. M., Chibanga, V., Shipanga, H., Parker, M. I."New insights from Whole Genome Sequencing: BCLAF1 deletion as a structural variant that predisposes cells towards cellular transformation". Oncology Reports 46, no. 4 (2021): 229. https://doi.org/10.3892/or.2021.8180