KRAS and BRAF mutations in circulating tumour DNA from locally advanced rectal cancer

Sclafani, F. et al. (2018) KRAS and BRAF mutations in circulating tumour DNA from locally advanced rectal cancer. Scientific Reports, 8, 1445. (doi: 10.1038/s41598-018-19212-5) (PMID:29362371) (PMCID:PMC5780472)

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There are limited data on circulating, cell-free, tumour (ct)DNA analysis in locally advanced rectal cancer (LARC). Digital droplet (dd)PCR was used to investigate KRAS/BRAF mutations in ctDNA from baseline blood samples of 97 LARC patients who were treated with CAPOX followed by chemoradiotherapy, surgery and adjuvant CAPOX ± cetuximab in a randomised phase II trial. KRAS mutation in G12D, G12V or G13D was detected in the ctDNA of 43% and 35% of patients with tumours that were mutant and wild-type for these hotspot mutations, respectively, according to standard PCR-based analyses on tissue. The detection rate in the ctDNA of 10 patients with less common mutations was 50%. In 26 cases ctDNA analysis revealed KRAS mutations that were not previously found in tissue. Twenty-two of these (84.6%) were detected following repeat tissue testing by ddPCR. Overall, the ctDNA detection rate in the KRAS mutant population was 66%. Detection of KRAS mutation in ctDNA failed to predict prognosis or refine patient selection for cetuximab. While this study confirms the feasibility of ctDNA analysis in LARC and the high sensitivity of ddPCR, larger series are needed to better address the role of ctDNA as a prognostic or predictive tool in this setting.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Braconi, Dr Chiara and Valeri, Dr Nicola
Authors: Sclafani, F., Chau, I., Cunningham, D., Hahne, J. C., Vlachogiannis, G., Eltahir, Z., Lampis, A., Braconi, C., Kalaitzaki, E., De Castro, D. G., Wotherspoon, A., Capdevila, J., Glimelius, B., Tarazona, N., Begum, R., Lote, H., Hulkki Wilson, S., Mentrasti, G., Brown, G., Tait, D., Oates, J., and Valeri, N.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Scientific Reports
Publisher:Nature Publishing Group
ISSN (Online):2045-2322
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Scientific Reports 8: 1445
Publisher Policy:Reproduced under a Creative Commons License

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