کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8646180 | 1570072 | 2018 | 30 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Identification of a MYCN and Wnt-related VANGL2-ITLN1 fusion gene in neuroblastoma
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کلمات کلیدی
LiClVangl2PCPRNA-seqORFMYCN - SRCT مشاهدهGenomic rearrangements - بازسازی ژنومیکGiant - غولopen reading frame - قاب خواندن بازPlanar Cell Polarity - قطبش پلانارlithium chloride - لیتیم کلریدUTR یا untranslated regions - منطقه ترجمه نشدهuntranslated region - منطقه غیر ترجمهNeuroblastoma - نوروبلاستوماPrecision medicine - پزشکی دقیقFusion gene - ژن فیوژنGenomics - ژنومیکCOSMIC - کاسمیکchromothripsis - کروماتریپس
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
ژنتیک
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The genomic fusion of two genes can lead to the expression of a fusion protein that can have oncogenic potential. The important contribution of such fusion genes to oncogenesis and tumour progression is being increasingly recognised. Here we report the presence of a novel VANGL2-ITLN1 fusion gene in the IMR32 neuroblastoma cell line. The fusion gene was identified by applying FusionHunter analysis to neuroblastoma cell line RNA sequencing data. This fusion results in the dramatic overexpression of a fusion transcript incorporating the full length ITLN1 coding sequence. Furthermore, the tumour expression levels of both components of the fusion gene (ITLN1 and VANGL2) are predictive of neuroblastoma patient outcome. High ITLN1 expression levels correlate with worse outcome across all neuroblastoma tumour stages and across MYCN amplification statuses. Survival probability was markedly worse for patients with both elevated MYCN and ITLN1 expression. We show that the VANGL2-ITLN1 fusion transcript can be transcriptionally upregulated upon lithium chloride (LiCl) treatment, a known agonist of the Wnt signalling pathway. The novel VANGL2-ITLN1 fusion is associated with regulatory networks such as MYCN, ALK and the Wnt/Planar Cell Polarity (PCP) pathway which are key regulators of neuroblastoma outcome. We reveal novel putative multilevel-interactions between the fusion gene components and the MYCN oncogene, including MYCN ITLN protein-protein interactions. Through its interactions with other oncogenes the VANGL2-ITLN1 fusion gene is likely to be involved in driving neuroblastoma progression and poor patient outcomes.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Gene Reports - Volume 12, September 2018, Pages 187-200
Journal: Gene Reports - Volume 12, September 2018, Pages 187-200
نویسندگان
David J. Duffy, Anja Konietzny, Aleksandar Krstic, Jai Prakash Mehta, Melinda Halasz, Walter Kolch,