%0 Journal Article
%A Yang, Rongxi
%A Pfütze, Katrin
%A Zucknick, Manuela
%A Sutter, Christian
%A Wappenschmidt, Barbara
%A Marme, Frederik
%A Qu, Bin
%A Cuk, Katarina
%A Engel, Christoph
%A Schott, Sarah
%A Schneeweiss, Andreas
%A Brenner, Hermann
%A Claus, Rainer
%A Plass, Christoph
%A Bugert, Peter
%A Hoth, Markus
%A Sohn, Christof
%A Schmutzler, Rita
%A Bartram, Claus R
%A Burwinkel, Barbara
%T DNA methylation array analyses identified breast cancer-associated HYAL2 methylation in peripheral blood.
%J International journal of cancer
%V 136
%N 8
%@ 0020-7136
%C Bognor Regis
%I Wiley-Liss
%M DKFZ-2017-03842
%P 1845 - 1855
%D 2015
%X Breast 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.
%K Biomarkers, Tumor (NLM Chemicals)
%K Cell Adhesion Molecules (NLM Chemicals)
%K GPI-Linked Proteins (NLM Chemicals)
%K Hyal2 protein, human (NLM Chemicals)
%K Hyaluronoglucosaminidase (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:25213452
%R 10.1002/ijc.29205
%U https://inrepo02.dkfz.de/record/127820