Novel candidate genes may be possible predisposing factors revealed by whole exome sequencing in familial esophageal squamous cell carcinoma

Forouzanfar, N. and Baranova, A. and Milanizadeh, S. and Heravi-Moussavi, A. and Jebelli, A. and Abbaszadegan, M. R. (2017) Novel candidate genes may be possible predisposing factors revealed by whole exome sequencing in familial esophageal squamous cell carcinoma. Tumor Biology, 39 (5).

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Abstract

Esophageal squamous cell carcinoma is one of the deadliest of all the cancers. Its metastatic properties portend poor prognosis and high rate of recurrence. A more advanced method to identify new molecular biomarkers predicting disease prognosis can be whole exome sequencing. Here, we report the most effective genetic variants of the Notch signaling pathway in esophageal squamous cell carcinoma susceptibility by whole exome sequencing. We analyzed nine probands in unrelated familial esophageal squamous cell carcinoma pedigrees to identify candidate genes. Genomic DNA was extracted and whole exome sequencing performed to generate information about genetic variants in the coding regions. Bioinformatics software applications were utilized to exploit statistical algorithms to demonstrate protein structure and variants conservation. Polymorphic regions were excluded by false-positive investigations. Gene-gene interactions were analyzed for Notch signaling pathway candidates. We identified novel and damaging variants of the Notch signaling pathway through extensive pathway-oriented filtering and functional predictions, which led to the study of 27 candidate novel mutations in all nine patients. Detection of the trinucleotide repeat containing 6B gene mutation (a slice site alteration) in five of the nine probands, but not in any of the healthy samples, suggested that it may be a susceptibility factor for familial esophageal squamous cell carcinoma. Noticeably, 8 of 27 novel candidate gene mutations (e.g. epidermal growth factor, signal transducer and activator of transcription 3, MET) act in a cascade leading to cell survival and proliferation. Our results suggest that the trinucleotide repeat containing 6B mutation may be a candidate predisposing gene in esophageal squamous cell carcinoma. In addition, some of the Notch signaling pathway genetic mutations may act as key contributors to esophageal squamous cell carcinoma. © The Author(s) 2017.

Item Type: Article
Additional Information: Cited By :1 Export Date: 16 February 2020 CODEN: TUMBE Correspondence Address: Abbaszadegan, M.R.; Medical Genetics Research Center, Faculty of Medicine, Mashhad University of Medical SciencesIran; email: Abbaszadeganmr@mums.ac.ir
Uncontrolled Keywords: Esophageal squamous cell carcinoma Notch signaling pathway Predisposing factor Whole exome sequencing epidermal growth factor genomic DNA growth differentiation factor 15 Notch receptor scatter factor receptor tumor marker tumor protein adult aged AKT1 gene Article bioinformatics cancer staging cancer susceptibility cell proliferation cell survival clinical article controlled study EGF gene female GDF15 gene gene gene interaction gene mutation gene sequence genetic association genetic predisposition genetic variability human informed consent male MET gene middle aged priority journal signal transduction trinucleotide repeat esophagus tumor exome genetic association study genetics genomics high throughput sequencing mutation pathology pedigree prognosis squamous cell carcinoma Biomarkers, Tumor Carcinoma, Squamous Cell Esophageal Neoplasms Genetic Association Studies Genetic Predisposition to Disease High-Throughput Nucleotide Sequencing Humans Neoplasm Proteins Receptors, Notch
Subjects: QZ pathology-neoplasms-Genetics
Divisions: Mashhad University of Medical Sciences
Depositing User: mr lib3 lib3
Date Deposited: 12 May 2020 08:36
Last Modified: 12 May 2020 08:36
URI: http://eprints.mums.ac.ir/id/eprint/16821

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