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  • Promoter hypermethylation inactivate tumor suppressor FAM134B and is associated with poor prognosis in colorectal cancer

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    Author(s)
    Islam, Farhadul
    Gopalan, Vinod
    Pillai, Suja
    Lu, Cu-tai
    Kasem, Kais
    Lam, Alfred King-yin
    Griffith University Author(s)
    Lam, Alfred K.
    Gopalan, Vinod
    Islam, Farhad
    Year published
    2018
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    Abstract
    The present study aims to examine promoter methylation status of FAM134B in a large cohort of patients with colorectal adenocarcinomas. The clinical significances and correlations of FAM134B promoter methylation with its expression are also analysed. Methylation‐specific high‐resolution melt‐curve analysis followed by sequencing was used to identify FAM134B promoter methylation in colorectal adenomas (N = 32), colorectal adenocarcinomas (N = 164), matched adjacent non‐neoplastic colorectal mucosae (N = 83) and colon cancer cell lines (N = 4). FAM134B expression was studied by real‐time quantitative polymerase chain reaction, ...
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    The present study aims to examine promoter methylation status of FAM134B in a large cohort of patients with colorectal adenocarcinomas. The clinical significances and correlations of FAM134B promoter methylation with its expression are also analysed. Methylation‐specific high‐resolution melt‐curve analysis followed by sequencing was used to identify FAM134B promoter methylation in colorectal adenomas (N = 32), colorectal adenocarcinomas (N = 164), matched adjacent non‐neoplastic colorectal mucosae (N = 83) and colon cancer cell lines (N = 4). FAM134B expression was studied by real‐time quantitative polymerase chain reaction, immunohistochemistry, and Western blots. FAM134B promoter methylation was more frequent in adenocarcinomas (52%; 85/164) when compared to that of adenomas (28%; 9/32) and non‐neoplastic mucosae (35%; 29/83). Cancer cells exhibited higher methylation when compared to non‐neoplastic cells. FAM134B promoter methylation was inversely correlated with low FAM134B copy number and mRNA/protein expressions, whereas in‐vitro demethylation has restored FAM134B expression in colon cancer cells. FAM134B promoter methylation was associated with high histological grade (P = .025), presence of peri‐neural infiltration (P = .012), lymphovascular invasion (P = .021), lymph node metastasis (P = .0001), distant metastasis (P = .0001) and advanced pathological stages (P = .0001). In addition, FAM134B promoter methylation correlated with cancer recurrence and poor survival rates of patients with colorectal adenocarcinomas. To conclude, FAM134B promoter methylation plays a key role in regulating FAM134B expression in vitro and in vivo, which in turn contributes to the prediction of the biological aggressiveness of colorectal adenocarcinomas. Furthermore, FAM134B methylation might act as a marker in predicting clinical prognosis in patients with colorectal adenocarcinomas.
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    Journal Title
    Genes, Chromosomes & Cancer
    Volume
    57
    Issue
    5
    DOI
    https://doi.org/10.1002/gcc.22525
    Copyright Statement
    © 2018 Wiley Periodicals Inc. This is the peer reviewed version of the following article: Promoter hypermethylation inactivate tumor suppressor FAM134B and is associated with poor prognosis in colorectal cancer, Genes, Chromosomes and Cancer, Volume 57, Issue 5, Pages 240-251, 2018 which has been published in final form at https://doi.org/10.1002/gcc.22525. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving (http://olabout.wiley.com/WileyCDA/Section/id-828039.html)
    Subject
    Oncology and carcinogenesis
    Oncology and carcinogenesis not elsewhere classified
    Publication URI
    http://hdl.handle.net/10072/380302
    Collection
    • Journal articles

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