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Circulating tumour DNA as a biomarker of genetics alterations in cancer

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Circulating tumour DNA as a biomarker of genetics alterations in cancer. Application to the quantitative determination of KRAS and BRAF mutations in plasma of colorectal cancer patients.

The pressing need to determine the KRAS mutational status for selecting patients with colorectal cancer for anti-EGFR therapy provides a great opportunity to use circulating tumor DNA (ctDNA) as a theranostic tool. However the determination of genetic alteration in ctDNA could benefit of a better knowledge of ctDNA, especially at the structural level.

We accumulated data on ctDNA structural characteristics enabling us to develop a specific ctDNA methodology. Intplex is based on Allele Specific Blocker Q-PCR, and consequently is simple, fast, and cost effective, and can discriminate targeted point mutation from even single copies of ctDNA. KRAS and BRAF mutations are driven mutations in CRC (colorectal cancer) and affect treatment outcome. Intplex was adapted to detect seven KRAS (G12V, G12D , G13D, G12S , G12A, G12C , G12R) and one BRAF V600E point mutations. KRAS and BRAF mutational status was determined with high concordance when comparing ctDNA analysis and conventional methods from tumor tissue section, and greater sensitivity (0.01% mutant/WT ratio).

We showed that CRC plasma analysis could replace advantageously tumour-section analysis of targeted point mutation and expand the scope of personalized medicine for cancer patients.

Hosted by Nitzan Rosenfeld

This talk is part of the Seminars on Quantitative Biology @ CRUK Cambridge Institute series.

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