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Circulating Cell-Free DNA from Colorectal Cancer Patients May Reveal High KRAS or BRAF Mutation Load
Abstract : We used a novel method based on allele-specific quantitative polymerase chain reaction (Intplex) for the analysis of circulating cell.free DNA (ccfDNA) to compare total ccfDNA and KRAS- or BRAF-mutated ccfDNA concentrations in blood samples from mice xenografted with the human SW620 colorectal cancer (CRC) cell line and from patients with CRC. Intplex enables single-copy detection of variant alleles down to a sensitivity of ≥0.005 mutant to wild-type ratio. The proportion of mutant allele corresponding to the percentage of tumor-derived ccfDNA was elevated in xenografted mice with KRAS homozygous mutation and varied highly from 0.13% to 68.7% in samples from mutation-positive CRC patients (n = 38). Mutant ccfDNA alleles were quantified in the plasma of every patient at stages II/III and IV with a mean of 8.4% (median, 8.4%) and 21.8% (median, 12.4%), respectively. Twelve of 38 (31.6%) and 5 of 38 (13.2%) samples showed a mutation load higher than 25%and 50%, respectively. This suggests that an important part of ccfDNA may originate from tumor cells. In addition, we observed that tumor-derived (mutant) ccfDNA was more fragmented than ccfDNA from normal tissues. This observation suggests that the form of tumor-derived and normal ccfDNA could differ. Our approach revealed that allelic dilution is much less pronounced than previously stated, considerably facilitating the noninvasive molecular analysis of tumors.
Littérature citée [31 références]
https://hal-unilim.archives-ouvertes.fr/hal-01826199
Contributeur : Philippe Sindou Connectez-vous pour contacter le contributeur
Soumis le : vendredi 29 juin 2018 - 10:47:36
Dernière modification le : jeudi 16 décembre 2021 - 14:24:40
Archivage à long terme le : : jeudi 27 septembre 2018 - 07:10:37
Contributeur : Philippe Sindou Connectez-vous pour contacter le contributeur
Soumis le : vendredi 29 juin 2018 - 10:47:36
Dernière modification le : jeudi 16 décembre 2021 - 14:24:40
Archivage à long terme le : : jeudi 27 septembre 2018 - 07:10:37
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PIIS1936523313800836.pdf
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