https://scholars.lib.ntu.edu.tw/handle/123456789/518182
標題: | Whole-Exome Sequencing of Nasopharyngeal Carcinoma Families Reveals Novel Variants Potentially Involved in Nasopharyngeal Carcinoma | 作者: | Yu G Hsu W.-L Coghill A.E Yu K.J CHENG-PING WANG PEI-JEN LOU Liu Z Jones K Vogt A Wang M Mbulaiteye S.M Chen H.-H Boland J Yeager M Diehl S.R Chen C.-J Hildesheim A Goldstein A.M. |
公開日期: | 2019 | 出版社: | Nature Publishing Group | 卷: | 9 | 期: | 1 | 來源出版物: | Scientific Reports | 摘要: | Genetic susceptibility is likely involved in nasopharyngeal carcinoma (NPC), a cancer caused by Epstein-Barr virus (EBV) infection. Understanding of genetic factors involved in NPC and how they contribute to EBV-induced carcinogenesis is limited. We conducted whole-exome capture/sequencing among 251 individuals from 97 multiplex families from Taiwan (205 affected, 21 obligate carriers, and 25 unaffected) using SeqCap EZ Human Exome Library v3.0 and Illumina HiSeq. Aligned sequences were filtered to identify likely-to-be-functional deleterious variants that co-segregated with disease. Ingenuity Pathway analysis was performed. Circulating magnesium levels were measured in 13 individuals in 2 families with NIPAL1 mutations and in 197 sporadic NPC cases and 237 controls. We identified variants in 12 genes likely involved in cancer pathogenesis, viral infection or immune responses to infection. These included genes postulated to be involved in magnesium transport (NIPAL1), EBV cell entry (ITGB6), modulation of EBV infection (BCL2L12, NEDD4L), telomere biology (CLPTM1L, BRD2, HNRNPU), modulation of cAMP signaling (RAPGEF3), DNA repair (PRKDC, MLH1), and Notch signaling (NOTCH1, DLL3). Pathway based analysis demonstrated enrichment for Notch signaling genes (p-value = 0.0006). Evaluation of individuals within NIPAL1 families suggested lower serum magnesium in NPC compared to unaffected members. A significant reduction in serum magnesium levels was observed among sporadic NPC cases compared to controls (7.1% NPC/1.7% controls below normal range; OR = 4.5; 95% CI = 1.4,14) and is consistent with findings demonstrating a role for magnesium channeling in T-cell responses to EBV. We identified novel genes associated with NPC that point to new areas of inquiry to better understand genetic factors that determine the fate of viral infections and/or otherwise predisposes to NPC. ? 2019, The Author(s). |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85068734834&doi=10.1038%2fs41598-019-46137-4&partnerID=40&md5=c3824358fd2723425e5e845eaf9631cd https://scholars.lib.ntu.edu.tw/handle/123456789/518182 |
ISSN: | 2045-2322 | DOI: | 10.1038/s41598-019-46137-4 | SDG/關鍵字: | tumor marker; adult; aged; case control study; female; follow up; gene expression regulation; genetic predisposition; genetics; human; male; middle aged; nasopharynx carcinoma; nasopharynx tumor; pathology; procedures; prognosis; single nucleotide polymorphism; very elderly; virus genome; whole exome sequencing; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Case-Control Studies; Female; Follow-Up Studies; Gene Expression Regulation, Neoplastic; Genetic Predisposition to Disease; Genome, Viral; Humans; Male; Middle Aged; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Polymorphism, Single Nucleotide; Prognosis; Whole Exome Sequencing |
顯示於: | 醫學系 |
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