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Logo of bmccancBioMed Centralsearchsubmit a manuscriptregisterthis articleBMC Cancer
BMC Cancer. 2012; 12: 244.
Published online Jun 13, 2012. doi:  10.1186/1471-2407-12-244
PMCID: PMC3437205
Methylation signature of lymph node metastases in breast cancer patients
Zeinab Barekati,1 Ramin Radpour,1 Qing Lu,2 Johannes Bitzer,3 Hong Zheng,4,5 Paolo Toniolo,6 Per Lenner,7 and Xiao Yan Zhongcorresponding author1
1Laboratory for Gynecological Oncology, Women’s Hospital/Department of Biomedicine, University of Basel, Hebelstrasse 20, CH 4031, Basel, Switzerland
2Department of Breast Surgery, West China Hospital/West China School of Medicine, Sichuan University, Chengdu, China
3Department of Obstetrics and Gynecology, Women’s Hospital, University of Basel, Schanzenstrasse 46, CH-4031, Basel, Switzerland
4Department of Oncology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital/West China School of Medicine, Sichuan University, Chengdu, China
5Laboratory of Molecular Diagnosis of Cancer, West China Hospital/West China School of Medicine, Sichuan University, Chengdu, China
6Department of Obstetrics & Gynecology, New York University School of Medicine / Institute Universitaire de Médecine Sociale et Preventive, CHUV, Rue du Bugnon 17, 1005, Lausanne, Switzerland
7Department of Oncology, Umeå University Hospital, Campus Area, S-90185, Umeå, Sweden
corresponding authorCorresponding author.
Zeinab Barekati: barekatiz/at/; Ramin Radpour: radpourr/at/; Qing Lu: zbarekati/at/; Johannes Bitzer: jbitzer/at/; Hong Zheng: hongzheng11/at/; Paolo Toniolo: Paolo.Toniolo/at/; Per Lenner: per.lenner/at/; Xiao Yan Zhong: zhongx/at/
Received November 25, 2011; Accepted May 31, 2012.
Invasion and metastasis are two important hallmarks of malignant tumors caused by complex genetic and epigenetic alterations. The present study investigated the contribution of aberrant methylation profiles of cancer related genes, APC, BIN1, BMP6, BRCA1, CST6, ESR-b, GSTP1, P14 (ARF), P16 (CDKN2A), P21 (CDKN1A), PTEN, and TIMP3, in the matched axillary lymph node metastasis in comparison to the primary tumor tissue and the adjacent normal tissue from the same breast cancer patients to identify the potential of candidate genes methylation as metastatic markers.
The quantitative methylation analysis was performed using the SEQUENOM’s EpiTYPER™ assay which relies on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS).
The quantitative DNA methylation analysis of the candidate genes showed higher methylation proportion in the primary tumor tissue than that of the matched normal tissue and the differences were significant for the APC, BIN1, BMP6, BRCA1, CST6, ESR-b, P16, PTEN and TIMP3 promoter regions (P<0.05). Among those candidate methylated genes, APC, BMP6, BRCA1 and P16 displayed higher methylation proportion in the matched lymph node metastasis than that found in the normal tissue (P<0.05). The pathway analysis revealed that BMP6, BRCA1 and P16 have a role in prevention of neoplasm metastasis.
The results of the present study showed methylation heterogeneity between primary tumors and metastatic lesion. The contribution of aberrant methylation alterations of BMP6, BRCA1 and P16 genes in lymph node metastasis might provide a further clue to establish useful biomarkers for screening metastasis.
Keywords: Methylation, Metastasis, Breast cancer, Biomarker
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