TY  - JOUR
AU  - Yang, Rongxi
AU  - Pfütze, Katrin
AU  - Zucknick, Manuela
AU  - Sutter, Christian
AU  - Wappenschmidt, Barbara
AU  - Marme, Frederik
AU  - Qu, Bin
AU  - Cuk, Katarina
AU  - Engel, Christoph
AU  - Schott, Sarah
AU  - Schneeweiss, Andreas
AU  - Brenner, Hermann
AU  - Claus, Rainer
AU  - Plass, Christoph
AU  - Bugert, Peter
AU  - Hoth, Markus
AU  - Sohn, Christof
AU  - Schmutzler, Rita
AU  - Bartram, Claus R
AU  - Burwinkel, Barbara
TI  - DNA methylation array analyses identified breast cancer-associated HYAL2 methylation in peripheral blood.
JO  - International journal of cancer
VL  - 136
IS  - 8
SN  - 0020-7136
CY  - Bognor Regis
PB  - Wiley-Liss
M1  - DKFZ-2017-03842
SP  - 1845 - 1855
PY  - 2015
AB  - 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.
KW  - Biomarkers, Tumor (NLM Chemicals)
KW  - Cell Adhesion Molecules (NLM Chemicals)
KW  - GPI-Linked Proteins (NLM Chemicals)
KW  - Hyal2 protein, human (NLM Chemicals)
KW  - Hyaluronoglucosaminidase (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:25213452
DO  - DOI:10.1002/ijc.29205
UR  - https://inrepo02.dkfz.de/record/127820
ER  -