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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-01-23

AUTHORS

Francesco Sclafani, Ian Chau, David Cunningham, Jens C. Hahne, George Vlachogiannis, Zakaria Eltahir, Andrea Lampis, Chiara Braconi, Eleftheria Kalaitzaki, David Gonzalez De Castro, Andrew Wotherspoon, Jaume Capdevila, Bengt Glimelius, Noelia Tarazona, Ruwaida Begum, Hazel Lote, Sanna Hulkki Wilson, Giulia Mentrasti, Gina Brown, Diana Tait, Jacqueline Oates, Nicola Valeri

ABSTRACT

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. More... »

PAGES

1445

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-018-19212-5

DOI

http://dx.doi.org/10.1038/s41598-018-19212-5

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1100485470

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29362371


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