title: Mutational analysis of circulating tumor cells from colorectal cancer patients and correlation with primary tumor tissue.
abstract: Circulating tumor cells (CTCs) provide a non-invasive accessible source of tumor material from patients with cancer. The cellular heterogeneity within CTC populations is of great clinical importance regarding the increasing number of adjuvant treatment options for patients with metastatic carcinomas, in order to eliminate residual disease. Moreover, the molecular profiling of these rare cells might lead to insight on disease progression and therapeutic strategies than simple CTCs counting. In the present study we investigated the feasibility to detect KRAS, BRAF, CD133 and Plastin3 (PLS3) mutations in an enriched CTCs cell suspension from patients with colorectal cancer, with the hypothesis that these genes` mutations are of great importance regarding the generation of CTCs subpopulations. Subsequently, we compared CTCs mutational status with that of the corresponding primary tumor, in order to access the possibility of tumor cells characterization without biopsy. CTCs were detected and isolated from blood drawn from 52 colorectal cancer (CRC) patients using a quantum-dot-labelled magnetic immunoassay method. Mutations were detected by PCR-RFLP or allele-specific PCR and confirmed by direct sequencing. In 52 patients, discordance between primary tumor and CTCs was 5.77% for KRAS, 3.85% for BRAF, 11.54% for CD133 rs3130, 7.69% for CD133 rs2286455 and 11.54% for PLS3 rs6643869 mutations. Our results support that DNA mutational analysis of CTCs may enable non-invasive, specific biomarker diagnostics and expand the scope of personalized medicine for cancer patients.
authors.affiliation: Department of Basic Medical Sciences, Laboratory of Biology, School of Medicine, University of Athens, Athens, Greece.
authors.forename: Anna
authors.initials: A
authors.lastname: Lyberopoulou
authors.affiliation: Second Department of Medical Oncology, Agioi Anargiroi Cancer Hospital, Kifisia, Athens, Greece.
authors.forename: Gerasimos
authors.initials: G
authors.lastname: Aravantinos
authors.affiliation: Second Department of Radiology, School of Medicine, University of Athens, Athens, Greece.
authors.forename: Efstathios P
authors.initials: EP
authors.lastname: Efstathopoulos
authors.affiliation: Second Department of Propedeutic Surgery, University of Athens School of Medicine, Laiko General Hospital, Athens, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Nikiteas
authors.affiliation: Institute of Nuclear and Radiological Sciences and Technology, Energy and Safety, N.C.S.R. 'Demokritos', Athens, Greece.
authors.forename: Penelope
authors.initials: P
authors.lastname: Bouziotis
authors.affiliation: Second Department of Medical Oncology, Agioi Anargiroi Cancer Hospital, Kifisia, Athens, Greece.
authors.forename: Athina
authors.initials: A
authors.lastname: Isaakidou
authors.affiliation: Exprerimental Research Center ELPEN Pharmaceuticals, Pikermi, Attiki, Greece.
authors.forename: Apostolos
authors.initials: A
authors.lastname: Papalois
authors.affiliation: Department of Basic Medical Sciences, Laboratory of Biology, School of Medicine, University of Athens, Athens, Greece.
authors.forename: Evangelos
authors.initials: E
authors.lastname: Marinos
authors.affiliation: Department of Basic Medical Sciences, Laboratory of Biology, School of Medicine, University of Athens, Athens, Greece; Second Department of Radiology, School of Medicine, University of Athens, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Gazouli
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D004252:DNA Mutational Analysis; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000378:metabolism* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor