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000127820 1001_ $$0P:(DE-He78)dd35af1fb84ec0812fe4bdea97d2f291$$aYang, Rongxi$$b0$$eFirst author$$udkfz
000127820 245__ $$aDNA methylation array analyses identified breast cancer-associated HYAL2 methylation in peripheral blood.
000127820 260__ $$aBognor Regis$$bWiley-Liss$$c2015
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000127820 520__ $$aBreast cancer (BC) is the leading cause of cancer-related mortality in women worldwide. Changes in DNA methylation in peripheral blood could be associated with malignancy at early stage. However, the BC-associated DNA methylation signatures in peripheral blood were largely unknown. Here, we performed a genome-wide methylation screening and identified a BC-associated differentially methylated CpG site cg27091787 in the hyaluronoglucosaminidase 2 gene (HYAL2) (discovery round with 72 BC case and 24 controls: p = 2.61 × 10(-9) adjusted for cell-type proportions). The substantially decreased methylation of cg27091787 in BC cases was confirmed in two validation rounds (first validation round with 338 BC case and 507 controls: p < 0.0001; second validation round with 189 BC case and 189 controls: p < 0.0001). In addition to cg27091787, the decreased methylation of a 650-bp CpG island shore of HYAL2 was also associated with increased risk of BC. Moreover, the expression and methylation of HYAL2 were inversely correlated with a p-value of 0.006. To note, the BC-associated decreased HYAL2 methylation was replicated in the T-cell fraction (p = 0.034). The cg27091787 methylation level enabled a powerful discrimination of early-stage BC cases (stages 0 and I) from healthy controls [area under curve (AUC) = 0.89], and was robust for the detection of BC in younger women as well (age < 50, AUC = 0.87). Our study reveals a strong association between decreased HYAL2 methylation in peripheral blood and BC, and provides a promising blood-based marker for the detection of early BC.
000127820 536__ $$0G:(DE-HGF)POF3-313$$a313 - Cancer risk factors and prevention (POF3-313)$$cPOF3-313$$fPOF III$$x0
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000127820 650_7 $$2NLM Chemicals$$aBiomarkers, Tumor
000127820 650_7 $$2NLM Chemicals$$aCell Adhesion Molecules
000127820 650_7 $$2NLM Chemicals$$aGPI-Linked Proteins
000127820 650_7 $$0EC 3.2.1.25$$2NLM Chemicals$$aHyal2 protein, human
000127820 650_7 $$0EC 3.2.1.35$$2NLM Chemicals$$aHyaluronoglucosaminidase
000127820 7001_ $$0P:(DE-He78)83906db1355a576371363a4b9f107d3d$$aPfütze, Katrin$$b1$$udkfz
000127820 7001_ $$0P:(DE-HGF)0$$aZucknick, Manuela$$b2
000127820 7001_ $$aSutter, Christian$$b3
000127820 7001_ $$aWappenschmidt, Barbara$$b4
000127820 7001_ $$aMarme, Frederik$$b5
000127820 7001_ $$aQu, Bin$$b6
000127820 7001_ $$0P:(DE-He78)0a8ada1f5d2ea05fc3af10cd808bfa9a$$aCuk, Katarina$$b7$$udkfz
000127820 7001_ $$aEngel, Christoph$$b8
000127820 7001_ $$aSchott, Sarah$$b9
000127820 7001_ $$aSchneeweiss, Andreas$$b10
000127820 7001_ $$0P:(DE-He78)90d5535ff896e70eed81f4a4f6f22ae2$$aBrenner, Hermann$$b11$$udkfz
000127820 7001_ $$0P:(DE-HGF)0$$aClaus, Rainer$$b12
000127820 7001_ $$0P:(DE-He78)4301875630bc997edf491c694ae1f8a9$$aPlass, Christoph$$b13$$udkfz
000127820 7001_ $$aBugert, Peter$$b14
000127820 7001_ $$aHoth, Markus$$b15
000127820 7001_ $$aSohn, Christof$$b16
000127820 7001_ $$aSchmutzler, Rita$$b17
000127820 7001_ $$aBartram, Claus R$$b18
000127820 7001_ $$0P:(DE-He78)15b7fd2bc02d5ef47a2fe2dd0140d2bf$$aBurwinkel, Barbara$$b19$$eLast author$$udkfz
000127820 773__ $$0PERI:(DE-600)1474822-8$$a10.1002/ijc.29205$$gVol. 136, no. 8, p. 1845 - 1855$$n8$$p1845 - 1855$$tInternational journal of cancer$$v136$$x0020-7136$$y2015
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