title: Driver Gene Mutations in Stools of Colorectal Carcinoma Patients Detected by Targeted Next-Generation Sequencing.
abstract: Detection of driver gene mutations in stool DNA represents a promising noninvasive approach for screening colorectal cancer (CRC). Amplicon-based next-generation sequencing (NGS) is a good option to study mutations in many cancer genes simultaneously and from a low amount of DNA. Our aim was to assess the feasibility of identifying mutations in 22 cancer driver genes with Ion Torrent technology in stool DNA from a series of 65 CRC patients. The assay was successful in 80% of stool DNA samples. NGS results showed 83 mutations in cancer driver genes, 29 hotspot and 54 novel mutations. One to five genes were mutated in 75% of cases. TP53, KRAS, FBXW7, and SMAD4 were the top mutated genes, consistent with previous studies. Of samples with mutations, 54% presented concomitant mutations in different genes. Phosphatidylinositol 3-kinase/mitogen-activated protein kinase pathway genes were mutated in 70% of samples, with 58% having alterations in KRAS, NRAS, or BRAF. Because mutations in these genes can compromise the efficacy of epidermal growth factor receptor blockade in CRC patients, identifying mutations that confer resistance to some targeted treatments may be useful to guide therapeutic decisions. In conclusion, the data presented herein show that NGS procedures on stool DNA represent a promising tool to detect genetic mutations that could be used in the future for diagnosis, monitoring, or treating CRC.
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Unit of Biological Anthropology, Department of Animal Biology, Plant Biology and Ecology, Autonomous University of Barcelona, Barcelona, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Armengol
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: Virinder K
authors.initials: VK
authors.lastname: Sarhadi
authors.affiliation: Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Ghanbari
authors.affiliation: Sasan Alborz Biomedical Research Center, Masoud Clinic, Tehran, Iran.
authors.forename: Masoud
authors.initials: M
authors.lastname: Doghaei-Moghaddam
authors.affiliation: Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran; Sasan Alborz Biomedical Research Center, Masoud Clinic, Tehran, Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Ansari
authors.affiliation: Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran; Sasan Alborz Biomedical Research Center, Masoud Clinic, Tehran, Iran.
authors.forename: Masoud
authors.initials: M
authors.lastname: Sotoudeh
authors.affiliation: Gastrointestinal Clinic, The University Central Hospital of Helsinki, Helsinki, Finland.
authors.forename: Pauli
authors.initials: P
authors.lastname: Puolakkainen
authors.affiliation: Gastrointestinal Clinic, The University Central Hospital of Helsinki, Helsinki, Finland.
authors.forename: Arto
authors.initials: A
authors.lastname: Kokkola
authors.affiliation: Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran; Sasan Alborz Biomedical Research Center, Masoud Clinic, Tehran, Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Malekzadeh
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Helsinki, Helsinki, Finland. Electronic address: sakari.knuutila@helsinki.fi.
authors.forename: Sakari
authors.initials: S
authors.lastname: Knuutila
mesh_terms: D014408:Biomarkers, Tumor; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D066246:ErbB Receptors / Q000235:genetics; D005243:Feces; D011905:Genes, ras; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D009154:Mutation; D009857:Oncogenes
chemical_list: D014408:Biomarkers, Tumor; D066246:ErbB Receptors