Next-generation sequencing identifies germline MRE11A variants as markers of radiotherapy outcomes in muscle-invasive bladder cancer

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Teo M.T.W., Dyrskjøt L., Nsengimana J., Buchwald C., Snowden H., Morgan J., Jensen J.B., Knowles M.A., Taylor G., Barrett J.H., Borre M., ørntoft T.F., Bishop D.T., Kiltie A.E.

Annals of Oncology 2014 25:4 (877-883) Article Number mdu014

Background: Muscle-invasive bladder cancer (MIBC) can be cured by radical radiotherapy (RT). We previously found tumour MRE11 expression to be predictive of survival following RT in MIBC, and this was independently validated in a separate institute.Here, we investigated germline MRE11A variants as possible predictors of RT outcomes in MIBC,using next-generation sequencing (NGS).Patients and methods: The MRE11A gene was amplified in germline DNA from 186 prospectively recruited MIBC patients treated with RT and sequenced using bar-coded multiplexed NGS.Germline variants were analysed for associations with cancer-specific survival (CSS).For validation as a prognostic or predictive marker, rs1805363 was then genotyped in a cystectomy-treated MIBC cohort of 256 individuals.MRE11A mRNA isoform expression was measured in bladder cancer cell lines and primary tumour samples…(ver más)

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