Abstract:
:Promoter region hypermethylation and transcriptional silencing is a frequent cause of tumour suppressor gene (TSG) inactivation in many human cancers. Previously, to identify candidate epigenetically inactivated TSGs in renal cell carcinoma (RCC), we monitored changes in gene expression in four RCC cell lines after treatment with the demethylating agent 5-azacytidine. This enabled us to identify HAI-2/SPINT2 as a novel epigenetically inactivated candidate RCC TSG. To identify further candidate TSGs, we undertook bioinformatic and molecular genetic evaluation of a further 60 genes differentially expressed after demethylation. In addition to HAI-2/SPINT2, four genes (PLAU, CDH1, IGFB3 and MT1G) had previously been shown to undergo promoter methylation in RCC. After bioinformatic prioritisation, expression and/or methylation analysis of RCC cell lines+/-primary tumours was performed for 34 genes. KRT19 and CXCL16 were methylated in RCC cell lines and primary RCC; however, 22 genes were differentially expressed after demethylation but did not show primary tumour-specific methylation (methylated in normal tissue (n=1); methylated only in RCC cell lines (n=9) and not methylated in RCC cell lines (n=12)). Re-expression of CXCL16 reduced growth of an RCC cell line in vitro. In a summary, a functional epigenomic analysis of four RCC cell lines using microarrays representing 11 000 human genes yielded both known and novel candidate TSGs epigenetically inactivated in RCC, suggesting that this is valid strategy for the identification of novel TSGs and biomarkers.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Morris MR,Gentle D,Abdulrahman M,Clarke N,Brown M,Kishida T,Yao M,Teh BT,Latif F,Maher ERdoi
10.1038/sj.bjc.6604180subject
Has Abstractpub_date
2008-01-29 00:00:00pages
496-501issue
2eissn
0007-0920issn
1532-1827pii
6604180journal_volume
98pub_type
杂志文章abstract::We have established a highly sensitive and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method to detect axillary lymph node metastases of breast cancer. Amplifying cytokeratin 19 (CK19) mRNA transcripts using real-time TaqMan PCR made it possible to quantify axillary metastatic burden. Metast...
journal_title:British journal of cancer
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journal_title:British journal of cancer
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pub_type: 杂志文章,meta分析
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journal_title:British journal of cancer
pub_type: 杂志文章,多中心研究
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pub_type: 杂志文章
doi:10.1038/s41416-019-0636-x
更新日期:2020-02-01 00:00:00
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