Promoter methylation correlates with reduced NDRG2 expression in advanced colon tumour View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2009-03-03

AUTHORS

Ada Piepoli, Rosa Cotugno, Giuseppe Merla, Annamaria Gentile, Bartolomeo Augello, Michele Quitadamo, Antonio Merla, Anna Panza, Massimo Carella, Rosalia Maglietta, Annarita D'Addabbo, Nicola Ancona, Saverio Fusilli, Francesco Perri, Angelo Andriulli

ABSTRACT

BACKGROUND: Aberrant DNA methylation of CpG islands of cancer-related genes is among the earliest and most frequent alterations in cancerogenesis and might be of value for either diagnosing cancer or evaluating recurrent disease. This mechanism usually leads to inactivation of tumour-suppressor genes. We have designed the current study to validate our previous microarray data and to identify novel hypermethylated gene promoters. METHODS: The validation assay was performed in a different set of 8 patients with colorectal cancer (CRC) by means quantitative reverse-transcriptase polymerase chain reaction analysis. The differential RNA expression profiles of three CRC cell lines before and after 5-aza-2'-deoxycytidine treatment were compared to identify the hypermethylated genes. The DNA methylation status of these genes was evaluated by means of bisulphite genomic sequencing and methylation-specific polymerase chain reaction (MSP) in the 3 cell lines and in tumour tissues from 30 patients with CRC. RESULTS: Data from our previous genome search have received confirmation in the new set of 8 patients with CRC. In this validation set six genes showed a high induction after drug treatment in at least two of three CRC cell lines. Among them, the N-myc downstream-regulated gene 2 (NDRG2) promoter was found methylated in all CRC cell lines. NDRG2 hypermethylation was also detected in 8 out of 30 (27%) primary CRC tissues and was significantly associated with advanced AJCC stage IV. Normal colon tissues were not methylated. CONCLUSION: The findings highlight the usefulness of combining gene expression patterns and epigenetic data to identify tumour biomarkers, and suggest that NDRG2 silencing might bear influence on tumour invasiveness, being associated with a more advanced stage. More... »

PAGES

11-11

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/1755-8794-2-11

DOI

http://dx.doi.org/10.1186/1755-8794-2-11

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1020757095

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/19257893


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16 schema:description BACKGROUND: Aberrant DNA methylation of CpG islands of cancer-related genes is among the earliest and most frequent alterations in cancerogenesis and might be of value for either diagnosing cancer or evaluating recurrent disease. This mechanism usually leads to inactivation of tumour-suppressor genes. We have designed the current study to validate our previous microarray data and to identify novel hypermethylated gene promoters. METHODS: The validation assay was performed in a different set of 8 patients with colorectal cancer (CRC) by means quantitative reverse-transcriptase polymerase chain reaction analysis. The differential RNA expression profiles of three CRC cell lines before and after 5-aza-2'-deoxycytidine treatment were compared to identify the hypermethylated genes. The DNA methylation status of these genes was evaluated by means of bisulphite genomic sequencing and methylation-specific polymerase chain reaction (MSP) in the 3 cell lines and in tumour tissues from 30 patients with CRC. RESULTS: Data from our previous genome search have received confirmation in the new set of 8 patients with CRC. In this validation set six genes showed a high induction after drug treatment in at least two of three CRC cell lines. Among them, the N-myc downstream-regulated gene 2 (NDRG2) promoter was found methylated in all CRC cell lines. NDRG2 hypermethylation was also detected in 8 out of 30 (27%) primary CRC tissues and was significantly associated with advanced AJCC stage IV. Normal colon tissues were not methylated. CONCLUSION: The findings highlight the usefulness of combining gene expression patterns and epigenetic data to identify tumour biomarkers, and suggest that NDRG2 silencing might bear influence on tumour invasiveness, being associated with a more advanced stage.
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23 schema:keywords AJCC stage IV
24 CRC cell lines
25 CRC tissues
26 CpG islands
27 DNA methylation
28 DNA methylation status
29 Myc
30 NDRG2
31 NDRG2 expression
32 NDRG2 hypermethylation
33 RNA expression profiles
34 aberrant DNA methylation
35 advanced AJCC stage IV
36 advanced colon tumors
37 advanced stage
38 alterations
39 analysis
40 biomarkers
41 bisulphite genomic sequencing
42 cancer
43 cancer-related genes
44 cancerogenesis
45 cell lines
46 chain reaction
47 chain reaction analysis
48 colon tissues
49 colon tumors
50 colorectal cancer
51 confirmation
52 current study
53 data
54 different sets
55 differential RNA expression profiles
56 disease
57 drug treatment
58 epigenetic data
59 expression
60 expression patterns
61 expression profiles
62 findings
63 frequent alterations
64 gene 2 promoter
65 gene expression patterns
66 gene promoter
67 genes
68 genome search
69 genomic sequencing
70 higher induction
71 hypermethylated gene promoters
72 hypermethylation
73 inactivation
74 induction
75 influence
76 invasiveness
77 islands
78 lines
79 means
80 means quantitative reverse-transcriptase polymerase chain reaction analysis
81 mechanism
82 methylation
83 methylation status
84 methylation-specific polymerase chain reaction
85 microarray data
86 new set
87 normal colon tissues
88 novel hypermethylated gene promoters
89 patients
90 patterns
91 polymerase chain reaction
92 polymerase chain reaction analysis
93 previous genome search
94 previous microarray data
95 primary CRC tissues
96 profile
97 promoter
98 promoter methylation
99 quantitative reverse transcriptase-polymerase chain reaction analysis
100 reaction
101 reaction analysis
102 recurrent disease
103 reduced NDRG2 expression
104 reverse transcriptase-polymerase chain reaction analysis
105 search
106 sequencing
107 set
108 stage
109 stage IV
110 status
111 study
112 tissue
113 treatment
114 tumor biomarkers
115 tumor invasiveness
116 tumor suppressor gene
117 tumor tissue
118 tumors
119 usefulness
120 validation
121 values
122 schema:name Promoter methylation correlates with reduced NDRG2 expression in advanced colon tumour
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