Sister chromatid exchange and genomic instability in soft tissue sarcomas: potential implications for response to DNA-damaging treatments

Salawu, Abdulazeez, Wright, Kristin, Al-Kathiri, Afnan, Wyld, Lynda, Reed, Malcolm and Sisley, Karen (2018) Sister chromatid exchange and genomic instability in soft tissue sarcomas: potential implications for response to DNA-damaging treatments. Sarcoma. ISSN 1357-714X

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Abstract

Sarcomas are rare heterogenous malignancies of mesenchymal origin characterised by complex karyotypes but no specific abnormalities. Recurrence is common and metastatic disease carries poor survival despite standard DNA-damaging radiotherapy or chemotherapy. DNA double strand breaks (DSB) are either repaired by mechanisms such as homologous recombination (HR); or result in cell death by apoptosis. Endogenous γH2AX and SCE formation are early and late events, respectively and their levels are considered surrogate measures of genomic instability. Combined γH2AX and SCE analysis were used to evaluate endogenous DNA DSB levels (and their subsequent repair) in 9 primary sarcoma cell lines and compared with well-established commercial lines. All the sarcoma cell lines had elevated γH2AX and SCE levels, but there was no correlation between the DNA DSB frequency and subsequent SCE. Typically radio-resistant osteosarcoma cells had relatively low γH2AX frequency, but high SCE counts suggestive of efficient DNA repair. Conversely, liposarcoma cells derived from a radio-sensitive tumour had high H2AX but relatively lower SCE levels that may imply inefficient DNA DSB repair. To our knowledge, this is the first report that correlates H2AX and SCE levels in primary sarcoma cell lines and may provide insight into potential response to DNA damaging-treatments.

Item Type: Article
Schools and Departments: Brighton and Sussex Medical School > Brighton and Sussex Medical School
Depositing User: Esme Acton-Stewart
Date Deposited: 22 Mar 2018 16:43
Last Modified: 04 Jul 2018 11:08
URI: http://sro.sussex.ac.uk/id/eprint/74597

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