Driver Gene Mutations in Stools of Colorectal Carcinoma Patients Detected by Targeted Next-Generation Sequencing
Armengol Rosell, Gemma (Universitat Autònoma de Barcelona. Departament de Biologia Animal, de Biologia Vegetal i d'Ecologia)
Sarhadi, Virinder K. (University of Helsinki. Department of Pathology)
Ghanbari, Reza (Tehran University of Medical Sciences)
Doghaei-Moghaddam, Masoud (Masoud Clinic (Tehran))
Ansari, Reza (Tehran University of Medical Sciences)
Sotoudeh, Masoud (Tehran University of Medical Sciences)
Puolakkainen, Pauli (The University Central Hospital of Helsinki)
Malekzadeh, Reza (Tehran University of Medical Sciences)
Knuutila, Sakari (The University of Helsinki. Department of Pathology)

Date:	2016
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.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió acceptada per publicar
Subject:	SDG 3 - Good Health and Well-being
Published in:	Journal of Molecular Diagnostics, Vol. 18, issue 4 (July 2016) , p. 471-479, ISSN 1943-7811

DOI: 10.1016/j.jmoldx.2016.01.008

Postprint 29 p, 1.1 MB

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