Academic Journal

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

التفاصيل البيبلوغرافية
العنوان: Novel candidate genes may be possible predisposing factors revealed by whole exome sequencing in familial esophageal squamous cell carcinoma
المؤلفون: Narjes Forouzanfar, Ancha Baranova, Saman Milanizadeh, Alireza Heravi-Moussavi, Amir Jebelli, Mohammad Reza Abbaszadegan
المصدر: Tumor Biology, Vol 39 (2017)
بيانات النشر: IOS Press, 2017.
سنة النشر: 2017
المجموعة: LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
مصطلحات موضوعية: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
الوصف: 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.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1423-0380
10104283
Relation: https://doaj.org/toc/1423-0380
DOI: 10.1177/1010428317699115
URL الوصول: https://doaj.org/article/d2f312ecc8834922983fcebae0c0493d
رقم الانضمام: edsdoj.2f312ecc8834922983fcebae0c0493d
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:14230380
10104283
DOI:10.1177/1010428317699115