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MiR-17-92 cluster is associated with 13q gain and c-myc expression during colorectal adenoma to adenocarcinoma progression.

Diosdado B, van de Wiel MA, Terhaar Sive Droste JS, Mongera S, Postma C, Meijerink WJ, Carvalho B, Meijer GA - Br. J. Cancer (2009)

Bottom Line: From the six members of the miR-17-92 cluster, all except miR-18a, showed significant increased expression in colorectal tumours with miR-17-92 locus gain compared with tumours without miR-17-92 locus gain.Unsupervised cluster analysis clustered the tumours based on the presence of miR-17-92 locus gain.Significant correlation between the expression of c-myc and the six miRNAs was also found.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, VU University medical center Amsterdam, Amsterdam 1081HV, the Netherlands.

ABSTRACT

Background: MicroRNAs are small non-coding RNA molecules, which regulate central mechanisms of tumorigenesis. In colorectal tumours, the combination of gain of 8q and 13q is one of the major factors associated with colorectal adenoma to adenocarcinoma progression. Functional studies on the miR-17-92 cluster localised on 13q31 have shown that its transcription is activated by c-myc, located on 8q, and that it has oncogenic activities. We investigated the contribution of the miR-17-92 cluster during colorectal adenoma to adenocarcinoma progression.

Methods: Expression levels of the miR-17-92 cluster were determined in 55 colorectal tumours and in 10 controls by real-time RT-PCR. Messenger RNA c-myc expression was also determined by real-time RT-PCR in 48 tumours with array comparative genomic hybridisation (aCGH) data available.

Results: From the six members of the miR-17-92 cluster, all except miR-18a, showed significant increased expression in colorectal tumours with miR-17-92 locus gain compared with tumours without miR-17-92 locus gain. Unsupervised cluster analysis clustered the tumours based on the presence of miR-17-92 locus gain. Significant correlation between the expression of c-myc and the six miRNAs was also found.

Conclusion: Increased expression of miR-17-92 cluster during colorectal adenoma to adenocarcinoma progression is associated to DNA copy number gain of miR17-92 locus on 13q31 and c-myc expression.

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Related in: MedlinePlus

Hierarchical cluster analysis of 48 colorectal tumours based on miR-17-92 cluster expression levels. Unsupervised cluster analysis of the expression levels of the six members of the miR-17-92 cluster across the 48 colorectal tumour groups separate the colorectal tumours with gain of the miR-17-92 locus (clusters 1 and 3) from the tumours with no gain at this locus (cluster 2). Each column represents a colorectal tumour and each row represents the expression of each of the components of the miR-17-92 cluster. Zero (0) represent colorectal tumours with no miR-17-92 locus gain and 1 represent colorectal tumours with miR-17-92 locus gain.
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fig3: Hierarchical cluster analysis of 48 colorectal tumours based on miR-17-92 cluster expression levels. Unsupervised cluster analysis of the expression levels of the six members of the miR-17-92 cluster across the 48 colorectal tumour groups separate the colorectal tumours with gain of the miR-17-92 locus (clusters 1 and 3) from the tumours with no gain at this locus (cluster 2). Each column represents a colorectal tumour and each row represents the expression of each of the components of the miR-17-92 cluster. Zero (0) represent colorectal tumours with no miR-17-92 locus gain and 1 represent colorectal tumours with miR-17-92 locus gain.

Mentions: Unsupervised hierarchical cluster analysis of the 48 tumours with aCGH data available, revealed three clusters on the basis of the expression levels of these six miRNAs (Figure 3). Significant association between cluster membership and DNA copy number status of the six miRNAs was found (P=0.001). Cluster 1 grouped three of samples with gain of miR17-92 locus. Cluster 2 comprised only four of the samples with gain of miR17-92 locus and 24 of the samples with no miR17-92 locus gain, whereas cluster 3 contained 10 of the samples with miR17-92 locus gain and seven of the tumours with no miR17-92 locus gain (Table 2).


MiR-17-92 cluster is associated with 13q gain and c-myc expression during colorectal adenoma to adenocarcinoma progression.

Diosdado B, van de Wiel MA, Terhaar Sive Droste JS, Mongera S, Postma C, Meijerink WJ, Carvalho B, Meijer GA - Br. J. Cancer (2009)

Hierarchical cluster analysis of 48 colorectal tumours based on miR-17-92 cluster expression levels. Unsupervised cluster analysis of the expression levels of the six members of the miR-17-92 cluster across the 48 colorectal tumour groups separate the colorectal tumours with gain of the miR-17-92 locus (clusters 1 and 3) from the tumours with no gain at this locus (cluster 2). Each column represents a colorectal tumour and each row represents the expression of each of the components of the miR-17-92 cluster. Zero (0) represent colorectal tumours with no miR-17-92 locus gain and 1 represent colorectal tumours with miR-17-92 locus gain.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2736819&req=5

fig3: Hierarchical cluster analysis of 48 colorectal tumours based on miR-17-92 cluster expression levels. Unsupervised cluster analysis of the expression levels of the six members of the miR-17-92 cluster across the 48 colorectal tumour groups separate the colorectal tumours with gain of the miR-17-92 locus (clusters 1 and 3) from the tumours with no gain at this locus (cluster 2). Each column represents a colorectal tumour and each row represents the expression of each of the components of the miR-17-92 cluster. Zero (0) represent colorectal tumours with no miR-17-92 locus gain and 1 represent colorectal tumours with miR-17-92 locus gain.
Mentions: Unsupervised hierarchical cluster analysis of the 48 tumours with aCGH data available, revealed three clusters on the basis of the expression levels of these six miRNAs (Figure 3). Significant association between cluster membership and DNA copy number status of the six miRNAs was found (P=0.001). Cluster 1 grouped three of samples with gain of miR17-92 locus. Cluster 2 comprised only four of the samples with gain of miR17-92 locus and 24 of the samples with no miR17-92 locus gain, whereas cluster 3 contained 10 of the samples with miR17-92 locus gain and seven of the tumours with no miR17-92 locus gain (Table 2).

Bottom Line: From the six members of the miR-17-92 cluster, all except miR-18a, showed significant increased expression in colorectal tumours with miR-17-92 locus gain compared with tumours without miR-17-92 locus gain.Unsupervised cluster analysis clustered the tumours based on the presence of miR-17-92 locus gain.Significant correlation between the expression of c-myc and the six miRNAs was also found.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, VU University medical center Amsterdam, Amsterdam 1081HV, the Netherlands.

ABSTRACT

Background: MicroRNAs are small non-coding RNA molecules, which regulate central mechanisms of tumorigenesis. In colorectal tumours, the combination of gain of 8q and 13q is one of the major factors associated with colorectal adenoma to adenocarcinoma progression. Functional studies on the miR-17-92 cluster localised on 13q31 have shown that its transcription is activated by c-myc, located on 8q, and that it has oncogenic activities. We investigated the contribution of the miR-17-92 cluster during colorectal adenoma to adenocarcinoma progression.

Methods: Expression levels of the miR-17-92 cluster were determined in 55 colorectal tumours and in 10 controls by real-time RT-PCR. Messenger RNA c-myc expression was also determined by real-time RT-PCR in 48 tumours with array comparative genomic hybridisation (aCGH) data available.

Results: From the six members of the miR-17-92 cluster, all except miR-18a, showed significant increased expression in colorectal tumours with miR-17-92 locus gain compared with tumours without miR-17-92 locus gain. Unsupervised cluster analysis clustered the tumours based on the presence of miR-17-92 locus gain. Significant correlation between the expression of c-myc and the six miRNAs was also found.

Conclusion: Increased expression of miR-17-92 cluster during colorectal adenoma to adenocarcinoma progression is associated to DNA copy number gain of miR17-92 locus on 13q31 and c-myc expression.

Show MeSH
Related in: MedlinePlus