KRAS and BRAF mutations in circulating tumour DNA from locally advanced rectal cancer.
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Embargo End Date
ICR Authors
Authors
Sclafani, F
Chau, I
Cunningham, D
Hahne, JC
Vlachogiannis, G
Eltahir, Z
Lampis, A
Braconi, C
Kalaitzaki, E
De Castro, DG
Wotherspoon, A
Capdevila, J
Glimelius, B
Tarazona, N
Begum, R
Lote, H
Hulkki Wilson, S
Mentrasti, G
Brown, G
Tait, D
Oates, J
Valeri, N
Chau, I
Cunningham, D
Hahne, JC
Vlachogiannis, G
Eltahir, Z
Lampis, A
Braconi, C
Kalaitzaki, E
De Castro, DG
Wotherspoon, A
Capdevila, J
Glimelius, B
Tarazona, N
Begum, R
Lote, H
Hulkki Wilson, S
Mentrasti, G
Brown, G
Tait, D
Oates, J
Valeri, N
Document Type
Journal Article
Date
2018-01-23
Date Accepted
2017-12-27
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.
Citation
Scientific reports, 2018, 8 (1), pp. 1445 - ?
Source Title
Publisher
NATURE PORTFOLIO
ISSN
2045-2322
eISSN
2045-2322
Research Team
Signal Transduction & Molecular Pharmacology
Medicine (RMH Smith Cunningham)
Evolutionary Genomics & Modelling
Gastrointestinal Cancer Biology and Genomics
Medicine (RMH Smith Cunningham)
Evolutionary Genomics & Modelling
Gastrointestinal Cancer Biology and Genomics