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Mutational landscape of plasma cell-free DNA identifies molecular features associated with therapeutic response in patients with colon cancer. A pilot study
K. Cervena, B. Pardini, M. Urbanova, S. Vodenkova, P. Eva, V. Veskrnova, M. Levy, T. Buchler, M. Mokrejs, A. Naccarati, P. Vodicka, V. Vymetalkova
Language English Country Great Britain
Document type Journal Article, Research Support, Non-U.S. Gov't
Grant support
NV17-30920A
MZ0
CEP Register
Digital library NLK
Full text - Article
NLK
Free Medical Journals
from 1996 to 1 year ago
Open Access Digital Library
from 1996-01-01
Medline Complete (EBSCOhost)
from 1996-01-01 to 1 year ago
- MeSH
- DNA, Neoplasm * MeSH
- Fluorouracil pharmacology MeSH
- Middle Aged MeSH
- Humans MeSH
- Mutation * MeSH
- Biomarkers, Tumor * MeSH
- Colonic Neoplasms blood diagnosis genetics therapy MeSH
- Prognosis MeSH
- Sequence Analysis, DNA MeSH
- Aged MeSH
- Neoplasm Staging MeSH
- Neoplasm Grading MeSH
- Cell-Free Nucleic Acids * MeSH
- High-Throughput Nucleotide Sequencing MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Cell-free DNA (cfDNA) has recently been used as a non-invasive diagnostic tool for detecting tumour-specific mutations. cfDNA may also be used for monitoring disease progression and treatment response, but so far researchers focused on one or few genes only. A genomic profile may provide better information on patient prognosis compared to single specific mutations. In this hypothesis-generating study, we profiled by whole exome sequencing serial plasma samples from 10 colon cancer (CC) patients collected before and after 5-fluorouracil-based therapy, and one year after diagnosis to determine alterations associated with treatment response. In parallel, genome profiling was also performed in patients' corresponding tumour tissue to ascertain the molecular landscape of resistant tumours. The mutation concordance between cfDNA and tumour tissue DNA was higher in more advanced tumour stages than in the early stages of the disease. In non-responders, a specific mutation profile was observed in tumour tissues (TPSD1 p.Ala92Thr, CPAMD8 p.Arg341Gln, OBP2A p.ArgTyr123CysHis). A pathogenic APC mutation (p.Ser1315Ter) was detected only in cfDNA of one poor responder one year after the diagnosis and after therapy termination. Another poor responder presented a likely pathogenic TP53 mutation (p.Arg110Pro) in cfDNA of all plasma samplings and in tumour tissue. In conclusion, cfDNA could be used for genetic characterisation of CC patients and might be clinically useful for non-invasive therapy response monitoring.
Candiolo Cancer Institute FPO IRCCS Sp142 Km3 95 100 60 Candiolo Turin Italy
Department of Surgery Thomayer University Hospital Videnska 800 140 59 Prague Czech Republic
IIGM Italian Institute for Genomic Medicine Sp142 Km3 95 100 60 Candiolo Turin Italy
References provided by Crossref.org
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