Researchers Utilize Circulating Tumor DNA to Analyze KRAS Mutations in Colorectal Cancer Patients with Liver Metastases

This past October at the European Society of Medical Oncology Congress 2018, a group of researchers from IMDL Genome Centre Bulgaria presented a poster focused on cell-free circulating tumor DNA with KRAS/EGFR mutations in metastatic colorectal cancer (mCRC) patients.

The emergence of KRAS mutation during the course of anti-EGFR (epidermal growth factor receptor) therapy is responsible for acquired resistance to treatment for mCRC patients. Circulating tumor DNA (ct-DNA) found in plasma samples is an alternative way to analyze KRAS mutations, with a concordance rate of up to 90%, as opposed to traditional tissue biopsy sampling.

The aim was to evaluate the RAS concordance rate between tissue and ct-DNA in mCRC patients. All blood samples were collected in cf-DNA/cf-RNA Preservative Tubes (Norgen Biotek Corp., Canada). ct-DNA extraction was performed with the Plasma/Serum cfc-DNA Purification Mini Kit (Norgen Biotek Corp., Canada). KRAS (ex. 2, codons 12 and 13) mutations on ct-DNA and tumor tissue were then detected by real-time PCR.

The group found that the estimated concordance rate between primary tumor and ct-DNA KRAS mutation analysis was 58%. The emergence of KRAS mutation in wild type patients revealed acquired resistance to anti-EGFR therapy. In addition to this, they found that patients with KRAS mutations on baseline ct-DNA, liver resection in responders, and liver metastases progressive disease in non-responders correlated with loss of KRAS mutation as a mechanism of acquired resistance to anti-angiogenesis treatment in the later.

Find the link to the abstract in Annals of Oncology here: https://doi.org/10.1093/annonc/mdy281.100

Kirov, A., Mihaylova, Z., Petrova, V., Todorov, T., Petkova, D., Garev, A., & Todorova-Georgieva, A. (2018). 554P KRAS-dependent and independent mechanisms of progressive disease (PD) in colorectal cancer (CRC) patients (pts) with liver metastases (LM) while monitoring on circulating cell free DNA (cfDNA). Annals of Oncology, 29(suppl_8), mdy281-100.

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