Methylation signature of lymph node metastases in breast cancer patients View Full Text


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Article Info

DATE

2012-06-13

AUTHORS

Zeinab Barekati, Ramin Radpour, Qing Lu, Johannes Bitzer, Hong Zheng, Paolo Toniolo, Per Lenner, Xiao Yan Zhong

ABSTRACT

BackgroundInvasion 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.MethodsThe 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).ResultsThe 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.ConclusionsThe 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. More... »

PAGES

244

References to SciGraph publications

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  • Identifiers

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    http://scigraph.springernature.com/pub.10.1186/1471-2407-12-244

    DOI

    http://dx.doi.org/10.1186/1471-2407-12-244

    DIMENSIONS

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    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/22695536


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    37 schema:description BackgroundInvasion 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.MethodsThe 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).ResultsThe 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.ConclusionsThe 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.
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    44 BIN1
    45 BMP6
    46 BRCA1
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    48 ConclusionsThe results
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    50 ESR
    51 EpiTYPER
    52 GSTP1
    53 P14
    54 PTEN
    55 Sequenom EpiTYPER
    56 TIMP3
    57 aberrant methylation profiles
    58 adjacent normal tissues
    59 alterations
    60 analysis
    61 axillary lymph node metastasis
    62 biomarkers
    63 breast cancer patients
    64 cancer
    65 cancer patients
    66 candidate gene methylation
    67 candidate genes
    68 candidates
    69 clues
    70 comparison
    71 contribution
    72 desorption/ionization time
    73 differences
    74 epigenetic alterations
    75 flight mass spectrometry
    76 further clues
    77 gene methylation
    78 genes
    79 hallmark
    80 heterogeneity
    81 important hallmark
    82 ionization time
    83 laser desorption/ionization time
    84 lesions
    85 lymph
    86 lymph node metastasis
    87 malignant tumors
    88 markers
    89 mass spectrometry
    90 matrix-assisted laser desorption/ionization time
    91 metastasis
    92 metastatic lesions
    93 metastatic markers
    94 methylation
    95 methylation alterations
    96 methylation analysis
    97 methylation heterogeneity
    98 methylation profiles
    99 methylation proportions
    100 methylation signatures
    101 neoplasm metastasis
    102 node metastasis
    103 normal tissues
    104 p16
    105 p16 gene
    106 p21
    107 pathway analysis
    108 patients
    109 potential
    110 present study
    111 prevention
    112 primary tumor
    113 primary tumor tissues
    114 profile
    115 promoter region
    116 proportion
    117 quantitative DNA methylation analysis
    118 quantitative methylation analysis
    119 region
    120 results
    121 role
    122 same breast cancer patients
    123 signatures
    124 spectrometry
    125 study
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