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Deregulation of ion channel and transporter encoding genes in pediatric gliomas.

Masselli M, Laise P, Tonini G, Fanelli D, Pillozzi S, Cetica V, Da Ros M, Sardi I, Buccoliero AM, Aricò M, Genitori L, Becchetti A, Arcangeli A - Front Oncol (2012)

Bottom Line: The correspondence between the two types of samples was statistically significant.Through a Functional Annotation Analysis (FAA) using the NIH-DAVID software, the DE genes turned out to be associated mainly with: immune/inflammatory response, cell proliferation and survival, cell adhesion and motility, neuronal phenotype, and ion transport.From FAA, we concluded that, among DE genes, pediatric gliomas show a strong deregulation of genes related to ion channels and transporters.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Pathology and Oncology, University of Firenze Firenze, Italy.

ABSTRACT
Brain tumors, including the majority gliomas, are the leading cause of cancer-related death in children. World Health Organization has divided pediatric brain tumors into different grades and, based upon cDNA microarray data identifying gene expression profiles (GEPs), it has become evident in the last decade that the various grades involve different types of genetic alterations. However, it is not known whether ion channel and transporter genes, intimately involved in brain functioning, are associated with such GEPs. We determined the GEPs in an available cohort of 10 pediatric brain tumors initially by comparing the data obtained from four primary tumor samples and corresponding short-term cultures. The correspondence between the two types of samples was statistically significant. We then performed bioinformatic analyses on those samples (a total of nine) which corresponded to tumors of glial origin, either tissues or cell cultures, depending on the best "RNA integrity number." We used R software to evaluate the genes which were differentially expressed (DE) in gliomas compared with normal brain. Applying a p-value below 0.01 and fold change ≥4, led to identification of 2284 DE genes. Through a Functional Annotation Analysis (FAA) using the NIH-DAVID software, the DE genes turned out to be associated mainly with: immune/inflammatory response, cell proliferation and survival, cell adhesion and motility, neuronal phenotype, and ion transport. We have shown that GEPs of pediatric brain tumors can be studied using either primary tumor samples or short-term cultures with similar results. From FAA, we concluded that, among DE genes, pediatric gliomas show a strong deregulation of genes related to ion channels and transporters.

No MeSH data available.


Related in: MedlinePlus

Heatmap of DE genes, performed, and plotted using “heatmap.2” function in R. Samples and genes (columns and rows respectively) are reordered on the basis of the average value of gene expression (log 2 ratio), and give rise to groups of genes and samples with similar average expression levels, according to the color key, shown on the top.
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Figure 2: Heatmap of DE genes, performed, and plotted using “heatmap.2” function in R. Samples and genes (columns and rows respectively) are reordered on the basis of the average value of gene expression (log 2 ratio), and give rise to groups of genes and samples with similar average expression levels, according to the color key, shown on the top.

Mentions: We determined the GEPs of nine gliomas, mainly LGGs (PAs, AG, AO, and E) and a GBM. Since the analysis mainly focused on glial-derived tumor, the AM sample was omitted. The Ambion® FirstChoice® Human Brain Reference RNA (Applied Biosystems, Life Technologies Corporation, USA), which derives from the pooling of 12 different donors and several brain regions, was used as the normal control reference. Although the tumor analyzed had different sites of presentation, we used a “whole brain” control sample, as previously described by Godard et al. (2003), to ensure a reproducible, tissue-specific reference. The expression profile of each gene was evaluated as detailed in Section “Materials and Methods.” In particular, a gene was assumed to be DE when the corrected p-value was lower than 0.01 and the fold change was ≥4. We obtained 2284 probes matching such requisites. The 2284 DE genes are shown in a cluster diagram in Figure 2 and are listed in Table S1 in Supplementary Material. About 1219 out of the 2284 DE genes (53%) were downregulated, whilst 1065 DE genes (47%) were upregulated (Figure 2).


Deregulation of ion channel and transporter encoding genes in pediatric gliomas.

Masselli M, Laise P, Tonini G, Fanelli D, Pillozzi S, Cetica V, Da Ros M, Sardi I, Buccoliero AM, Aricò M, Genitori L, Becchetti A, Arcangeli A - Front Oncol (2012)

Heatmap of DE genes, performed, and plotted using “heatmap.2” function in R. Samples and genes (columns and rows respectively) are reordered on the basis of the average value of gene expression (log 2 ratio), and give rise to groups of genes and samples with similar average expression levels, according to the color key, shown on the top.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3362739&req=5

Figure 2: Heatmap of DE genes, performed, and plotted using “heatmap.2” function in R. Samples and genes (columns and rows respectively) are reordered on the basis of the average value of gene expression (log 2 ratio), and give rise to groups of genes and samples with similar average expression levels, according to the color key, shown on the top.
Mentions: We determined the GEPs of nine gliomas, mainly LGGs (PAs, AG, AO, and E) and a GBM. Since the analysis mainly focused on glial-derived tumor, the AM sample was omitted. The Ambion® FirstChoice® Human Brain Reference RNA (Applied Biosystems, Life Technologies Corporation, USA), which derives from the pooling of 12 different donors and several brain regions, was used as the normal control reference. Although the tumor analyzed had different sites of presentation, we used a “whole brain” control sample, as previously described by Godard et al. (2003), to ensure a reproducible, tissue-specific reference. The expression profile of each gene was evaluated as detailed in Section “Materials and Methods.” In particular, a gene was assumed to be DE when the corrected p-value was lower than 0.01 and the fold change was ≥4. We obtained 2284 probes matching such requisites. The 2284 DE genes are shown in a cluster diagram in Figure 2 and are listed in Table S1 in Supplementary Material. About 1219 out of the 2284 DE genes (53%) were downregulated, whilst 1065 DE genes (47%) were upregulated (Figure 2).

Bottom Line: The correspondence between the two types of samples was statistically significant.Through a Functional Annotation Analysis (FAA) using the NIH-DAVID software, the DE genes turned out to be associated mainly with: immune/inflammatory response, cell proliferation and survival, cell adhesion and motility, neuronal phenotype, and ion transport.From FAA, we concluded that, among DE genes, pediatric gliomas show a strong deregulation of genes related to ion channels and transporters.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Pathology and Oncology, University of Firenze Firenze, Italy.

ABSTRACT
Brain tumors, including the majority gliomas, are the leading cause of cancer-related death in children. World Health Organization has divided pediatric brain tumors into different grades and, based upon cDNA microarray data identifying gene expression profiles (GEPs), it has become evident in the last decade that the various grades involve different types of genetic alterations. However, it is not known whether ion channel and transporter genes, intimately involved in brain functioning, are associated with such GEPs. We determined the GEPs in an available cohort of 10 pediatric brain tumors initially by comparing the data obtained from four primary tumor samples and corresponding short-term cultures. The correspondence between the two types of samples was statistically significant. We then performed bioinformatic analyses on those samples (a total of nine) which corresponded to tumors of glial origin, either tissues or cell cultures, depending on the best "RNA integrity number." We used R software to evaluate the genes which were differentially expressed (DE) in gliomas compared with normal brain. Applying a p-value below 0.01 and fold change ≥4, led to identification of 2284 DE genes. Through a Functional Annotation Analysis (FAA) using the NIH-DAVID software, the DE genes turned out to be associated mainly with: immune/inflammatory response, cell proliferation and survival, cell adhesion and motility, neuronal phenotype, and ion transport. We have shown that GEPs of pediatric brain tumors can be studied using either primary tumor samples or short-term cultures with similar results. From FAA, we concluded that, among DE genes, pediatric gliomas show a strong deregulation of genes related to ion channels and transporters.

No MeSH data available.


Related in: MedlinePlus