This is a basic science project, finding out more about how chromosome abnormalities in the nuclei of sarcoma cells might upset the regulation of cell turnover. If they can understand more about this it might be an opening to developing new approaches to treatment.
Sarcomas often have abnormalities in the chromosomes in tumour cell nuclei. In some forms of sarcoma, GIST for example, these chromosomal abnormalities play a major part in the development of the sarcoma and can even act as a marker to confirm the diagnosis and be a target for treatment. Imatanib was developed to treat GIST by targeting the C-kit receptor where a particular abnormality had been identified.
In other sarcomas like leiomyosarcoma the chromosomal abnormalities are more varied. Consistent patterns have not been identified. However, in an earlier study the researchers identified frequent chromosomal abnormalities in leiomyosarcomas and GIST which contain genes well known to be involved in the development of sarcomas, such as ataxia telangiectasia mutation (ATM) and retinoblastoma (RB) genes. These genes are important in regulatory mechanisms in the development of cancer, such as cell division and damage to DNA. The mutation of the ATM gene may be of particular importance as it could lead to new treatments.
Basically, people with ATMs are limited in the ability to repair DNA damage. A new class of drugs, PARP inhibitors, can knock out alternative DNA repair mechanisms. This might sound like a worse situation but in fact it means that with even fewer ways of repairing DNA, the cells might become much more susceptible to treatments such as radiotherapy.
- Salawu, A. et al. High quality genomic copy number data from archival formalin-fixed paraffin-embedded leiomyosarcoma: optimisation of universal linkage system labelling. PLoS One. 2012. 7, e50415.
- Salawu, A. et al. Establishment and molecular characterisation of seven novel soft-tissue sarcoma cell lines. British Journal of Cancer. October 2016. 115, 1058-1068(25).
- Salawu, A. et al. 'Genetic Characteristics of Soft Tissue Sarcoma' Presented at the British Sarcoma Group Conference, Oxford 29 February. 2 March 2012.
- Salawu, A. et al. 'Identification of soft tissue sarcoma subtypes using Microarray-based Comparative Genomic Hybridisation'. Presented at the 17th World congress on Advances in Oncology and 15th International Symposium on Molecular Medicine, Crete. 11-13 March 2012.
- Salawu, A. et al. Trio RhoGEF is associated with tumour progression in Undifferentiated Pleomorphic Sarcoma. Presented at the British Sarcoma Group Conference, Nottingham. 27 February 2014.
- Salawu, A. et al. Trio RhoGEF amplification a druggable target and potential biomarker in Undifferentiated Pleomorphic Sarcoma. Sarcoma Research Symposium (Basic Science). 8th September 2016. London.
- Salawu, A., Fernando, M., Hughes, D., Reed, M., Woll, P., & Sisley, K. (2017). One tumour, two clones: An in vitro model of intra-tumour heterogeneity. Presented at the European Society for Medical Oncology Congress September 2017 in Madrid, Spain. Published In Annals of Oncology. Vol. 28.
- Dr Abdulazeez Salawu submitted a thesis titled “Identification of Subtype-specific Pathogenetic Aberrations in Soft Tissue Sarcoma utilising High-resolution Genomic Copy Number Analysis” in May 2014. Following a successful viva, he was awarded the degree but the University of Sheffield in November 2014 with no corrections required.
- The University of Sheffield have made sarcoma cell lines available on a free basis to academics and not for profit organisations through a Material Transfer Agreements (MTA).