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Variant detection and personalized treatment in colorectal cancer
Background
Colorectal cancer, a type of malignancy in the colon or rectum, constitutes one of the most prevalent types of cancer, with high mortality rate. There are available different treatment options, like surgical removal, chemotherapy or targeted therapy. Detection of specific biomarkers or variants (mutations) provides important data for an efficient personalized treatment. Study of circulating tumor cells (CTCs), in combination with high-sensitivity assays, might contribute in more successful treatment protocols. In this study, we performed mutational analysis in healthy and colorectal cancer samples, to reveal potential patterns of variants, and to compare whether these variant types are different between differentiated colorectal cancer and CTCs.
Methods
Blood sample was isolated from five healthy individuals and ten patients with colorectal cancer at stage III or IV. For cancer cases, CTCs detected and isolated with Fluorescence-Activated Cell Sorting, while for normal individuals, peripheral blood mononuclear cells selected using density gradient centrifugation. In addition, six commercial human colorectal cancer cell lines were used. Genomic DNA isolated from all the above samples, and NGS protocol followed with Illumina’s TruSight Oncology 500 panel, and run on NextSeq 550 system. The analysis performed with Clinical Genomic Workspace, v6.15.1, powered by PierianDx.
Results
There were detected several variants with clinical significance, which were observed in cancer but not healthy samples. Among them, BRAF-V600E, was detected in the majority of patients’ CTCs but only in one commercial cell line, while the KRAS-G13D, detected in all cancer cell lines, but not in patient’s samples. Variants in genes PTCH1, RNF43 and BCORL1, presented in the majority of cancer cell lines but not in CTCs, while specific mutation in MET and BRCA1 detected in CTCs but not in commercial cell lines. The variant frequency in CTCs was lower than 10% in almost all cases analyzed.
Conclusions
These preliminary data demonstrated once again that CTCs do not exhibit the same characteristics as differentiated cancer cells, and therefore the treatment algorithm cannot be the same for both of them. The targeted therapies used in clinical routine, are not always beneficial for CTCs and vice versa. The use of powerful techniques, which can detect variants with low frequency, might contribute in beneficial medical care in cancer.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosures
I. Papasotiriou: Full / Part-time employment: R.G.C.C. INTERNATIONAL GMBH. All other authors have declared no conflicts of interest.
