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000143882 1001_ $$aSchmitt, Katrin$$b0
000143882 245__ $$aSomatic mutations and promotor methylation of the ryanodine receptor 2 is a common event in the pathogenesis of head and neck cancer.
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000143882 520__ $$aGenomic sequencing projects unraveled the mutational landscape of head and neck squamous cell carcinoma (HNSCC) and provided a comprehensive catalogue of somatic mutations. However, the limited number of significant cancer-related genes obtained so far only partially explains the biological complexity of HNSCC and hampers the development of novel diagnostic biomarkers and therapeutic targets. We pursued a multi-scale omics approach based on whole-exome sequencing, global DNA methylation and gene expression profiling data derived from tumor samples of the HIPO-HNC cohort (n=87), and confirmed new findings with datasets from The Cancer Genome Atlas (TCGA). Promoter methylation was confirmed by MassARRAY analysis and protein expression was assessed by immunohistochemistry and immunofluorescence staining. We discovered a set of cancer-related genes with frequent somatic mutations and high frequency of promoter methylation. This included the ryanodine receptor 2 (RYR2), which showed variable promoter methylation and expression in both tumor samples and cell lines. Immunohistochemical staining of tissue sections unraveled a gradual loss of RYR2 expression from normal mucosa via dysplastic lesion to invasive cancer, and indicated that reduced RYR2 expression in adjacent tissue and precancerous lesions might serve as risk factor for unfavorable prognosis and upcoming malignant conversion. In summary, our data indicate that impaired RYR2 function by either somatic mutation or epigenetic silencing is a common event in HNSCC pathogenesis. Detection of RYR2 expression and/or promoter methylation might enable risk assessment for malignant conversion of dysplastic lesions. This article is protected by copyright. All rights reserved.
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000143882 7001_ $$aMolfenter, Britta$$b1
000143882 7001_ $$0P:(DE-He78)b36816550a92f3d43063316f4ab83d2e$$aKoerich Laureano, Natalia$$b2
000143882 7001_ $$0P:(DE-He78)4f5721350bd23340e626cb0340bef47a$$aTawk, Bouchra$$b3
000143882 7001_ $$0P:(DE-He78)e247efc0264a7b0e4bae09804002d4e1$$aBieg, Matthias$$b4
000143882 7001_ $$0P:(DE-He78)d0227eb1849a4009d6b361aacc22c907$$aPastor Hostench, Xavier$$b5
000143882 7001_ $$0P:(DE-He78)ff4024f7bc236e7897d9c18ee19c451f$$aWeichenhan, Dieter$$b6
000143882 7001_ $$aUllrich, Nina D$$b7
000143882 7001_ $$aShang, Viny$$b8
000143882 7001_ $$0P:(DE-He78)29306fd3ae9f1a9839ed888ebc5c8074$$aRichter, Daniela$$b9
000143882 7001_ $$aStögbauer, Fabian$$b10
000143882 7001_ $$0P:(DE-He78)b12aaacaa142dabed85c6d84d00bf0fb$$aSchroeder, Lea$$b11
000143882 7001_ $$ade Bem Prunes, Bianca$$b12
000143882 7001_ $$aVisioli, Fernanda$$b13
000143882 7001_ $$aVarvaki Rados, Pantelis$$b14
000143882 7001_ $$aJou, Adriana$$b15
000143882 7001_ $$aPlath, Michaela$$b16
000143882 7001_ $$aFederspil, Philippe A$$b17
000143882 7001_ $$aThierauf, Julia$$b18
000143882 7001_ $$aDöscher, Johannes$$b19
000143882 7001_ $$aWeissinger, Stephanie E$$b20
000143882 7001_ $$aHoffmann, Thomas K$$b21
000143882 7001_ $$00000-0003-0873-1601$$aWagner, Steffen$$b22
000143882 7001_ $$aWittekindt, Claus$$b23
000143882 7001_ $$0P:(DE-He78)4096eeffdfc73b75e8ba63dc621a017d$$aIshaque, Naveed$$b24
000143882 7001_ $$0P:(DE-He78)78b6aa82148e60b4d91e3a37a6d3d9a0$$aEils, Roland$$b25
000143882 7001_ $$aKlussmann, Jens P$$b26
000143882 7001_ $$0P:(DE-He78)d84ca2cd7f160904c387ee699735076c$$aHolzinger, Dana$$b27
000143882 7001_ $$0P:(DE-He78)4301875630bc997edf491c694ae1f8a9$$aPlass, Christoph$$b28
000143882 7001_ $$0P:(DE-He78)360c5bc2b71a849e35aca747c041dda7$$aAbdollahi, Amir$$b29
000143882 7001_ $$aFreier, Kolja$$b30
000143882 7001_ $$0P:(DE-He78)891da714b7f7991d9c4c1d5224c991e7$$aWeichert, Wilko$$b31$$udkfz
000143882 7001_ $$aZaoui, Karim$$b32
000143882 7001_ $$0P:(DE-He78)2e5f34f1c58eda4787a14c9dc139ca5f$$aHess, Jochen$$b33$$eLast author
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