Plasma clearance of RAS mutation under therapeutic pressure is a rare event in metastatic colorectal cancer.
Adaptor Proteins, Signal Transducing
/ genetics
Adult
Aged
Aged, 80 and over
Antineoplastic Agents
/ therapeutic use
Biomarkers, Tumor
/ blood
Circulating Tumor DNA
/ analysis
Colorectal Neoplasms
/ blood
DNA Methylation
High-Throughput Nucleotide Sequencing
Humans
Male
Middle Aged
Mutation
Neoplasm Metastasis
Polymerase Chain Reaction
Prospective Studies
Proto-Oncogene Proteins p21(ras)
/ genetics
RAS mutations
circulating tumor DNA
droplet-based digital PCR
metastatic colorectal cancer
next-generation sequencing
Journal
International journal of cancer
ISSN: 1097-0215
Titre abrégé: Int J Cancer
Pays: United States
ID NLM: 0042124
Informations de publication
Date de publication:
15 08 2020
15 08 2020
Historique:
received:
08
05
2019
revised:
19
07
2019
accepted:
30
07
2019
pubmed:
1
9
2019
medline:
7
4
2021
entrez:
1
9
2019
Statut:
ppublish
Résumé
In metastatic colorectal cancer (mCRC), circulating tumor DNA (ctDNA) monitoring can be used to genotype tumors and track clonal evolution. We investigated the clearance of RAS mutated clones under chemotherapy pressure by ctDNA analysis in patients with a RAS mutated mCRC. Patients with a RAS mutated tumor included in the prospective PLACOL study were monitored for ctDNA. Analyses were based on optimized targeted next-generation sequencing and/or droplet-based digital polymerase chain reaction (ddPCR). For plasma samples without detectable mutations at progression disease, we tested the methylation status of WIF1 and NPY genes using methylation-ddPCR (met-ddPCR) to validate the presence of ctDNA. Among the 36 patients with positive plasma samples for RAS mutations at inclusion, 28 (77.8%) remained RAS positive at disease progression and 8 (22.2%) became negative. Subsequent met-ddPCR for methylated markers showed that only two out of the eight patients with RAS negative plasma had detectable ctDNA at progression. Therefore, only 2 samples among 36 were confirmed for clearance of RAS mutation in our series. In conclusion, this study suggests that the clearance of RAS mutations in patients treated by chemotherapy for a RAS mutated mCRC is a rare event. Monitoring tumor mutations in plasma samples should be combined with a strict control of the presence of ctDNA. The therapeutic impacts of RAS clearance need to be further explored.
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Antineoplastic Agents
0
Biomarkers, Tumor
0
Circulating Tumor DNA
0
KRAS protein, human
0
WIF1 protein, human
0
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1185-1189Informations de copyright
© 2019 UICC.
Références
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