Limits...
Associating GWAS Information with the Notch Signaling Pathway Using Transcription Profiling.

Hicks C, Pannuti A, Miele L - Cancer Inform (2011)

Bottom Line: However, they offer limited insights about the biological mechanisms by which SNPs confer risk.We then investigated their expression, along with 32 genes involved in the Notch signaling pathway using two publicly available gene expression data sets from the Caucasian (42 cases and 143 controls) and Asian (43 cases and 43 controls) populations.Pathway prediction and network modeling confirmed that Notch receptors and genes involved in the Notch signaling pathway interact with genes containing SNPs associated with risk for breast cancer.

View Article: PubMed Central - PubMed

Affiliation: Cancer Institute, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA.

ABSTRACT
Genome-wide association studies (GWAS) have identified SNPs associated with breast cancer. However, they offer limited insights about the biological mechanisms by which SNPs confer risk. We investigated the association of GWAS information with a major oncogenic pathway in breast cancer, the Notch signaling pathway. We first identified 385 SNPs and 150 genes associated with risk for breast cancer by mining data from 41 GWAS. We then investigated their expression, along with 32 genes involved in the Notch signaling pathway using two publicly available gene expression data sets from the Caucasian (42 cases and 143 controls) and Asian (43 cases and 43 controls) populations. Pathway prediction and network modeling confirmed that Notch receptors and genes involved in the Notch signaling pathway interact with genes containing SNPs associated with risk for breast cancer. Additionally, we identified other SNP-associated biological pathways relevant to breast cancer, including the P53, apoptosis and MAP kinase pathways.

No MeSH data available.


Related in: MedlinePlus

Results of pathway prediction and network modeling showing interactions between genes containing SNPs associated with risk for breast cancer and genes involved in the Notch signaling and other biological pathways. The results are based on genes containing SNPs with the largest effect size (P < 10−5). Nodes represent genes and vertices represent interactions. The color code denotes the biological process in which the genes are involved as defined in Figure 3. The color codes in the vertices indicate the experimental techniques or a combination thereof used to confirm the relationship between the genes as determined by the experiments reported in the literature. Candidate genes containing SNPs associated with risk for breast cancer are shown in red, genes involved in the Notch signaling pathway are shown in blue and novel genes are shown in black.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3091413&req=5

f7-cin-2011-093: Results of pathway prediction and network modeling showing interactions between genes containing SNPs associated with risk for breast cancer and genes involved in the Notch signaling and other biological pathways. The results are based on genes containing SNPs with the largest effect size (P < 10−5). Nodes represent genes and vertices represent interactions. The color code denotes the biological process in which the genes are involved as defined in Figure 3. The color codes in the vertices indicate the experimental techniques or a combination thereof used to confirm the relationship between the genes as determined by the experiments reported in the literature. Candidate genes containing SNPs associated with risk for breast cancer are shown in red, genes involved in the Notch signaling pathway are shown in blue and novel genes are shown in black.

Mentions: To further address the problem of reliability of GWAS data, we performed additional analyses combining genes containing SNPs replicated in multiple independent studies with genes involved in the Notch Signaling pathway. Genes containing SNPs reported in multiple independent studies included A2BP1, ADH1B, ALPL, ATM, BLM, CASP8, CCND1, CDKN1A, CHEK1, CSB, PMBT1, ECHDC1, EHMT, ERBB4, ESR1, FANCA, FGFR2, HCN1, ICAM5, IGF1, IGFIR, IGFBP3, KU80, LSP1, MGMT, MSH2, NEIL2, POLB, POLK, RAD51L1, RB1, RNF146, RPA1, RPA2, SKAP2, SOD2, MAP3K1, H19, TOX3, TGFB1, TNP1, XPA, XPC, XRCC3, XRCC4. The results are shown in Figure 7. We found that genes containing SNPs replicated in multiple independent studies interact with each other and with genes involved in the Notch signaling pathway, and genes involved in other breast cancer-relevant biological pathways. In addition, we identified novel genes not yet identified by GWAS (genes shown in black).


Associating GWAS Information with the Notch Signaling Pathway Using Transcription Profiling.

Hicks C, Pannuti A, Miele L - Cancer Inform (2011)

Results of pathway prediction and network modeling showing interactions between genes containing SNPs associated with risk for breast cancer and genes involved in the Notch signaling and other biological pathways. The results are based on genes containing SNPs with the largest effect size (P < 10−5). Nodes represent genes and vertices represent interactions. The color code denotes the biological process in which the genes are involved as defined in Figure 3. The color codes in the vertices indicate the experimental techniques or a combination thereof used to confirm the relationship between the genes as determined by the experiments reported in the literature. Candidate genes containing SNPs associated with risk for breast cancer are shown in red, genes involved in the Notch signaling pathway are shown in blue and novel genes are shown in black.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3091413&req=5

f7-cin-2011-093: Results of pathway prediction and network modeling showing interactions between genes containing SNPs associated with risk for breast cancer and genes involved in the Notch signaling and other biological pathways. The results are based on genes containing SNPs with the largest effect size (P < 10−5). Nodes represent genes and vertices represent interactions. The color code denotes the biological process in which the genes are involved as defined in Figure 3. The color codes in the vertices indicate the experimental techniques or a combination thereof used to confirm the relationship between the genes as determined by the experiments reported in the literature. Candidate genes containing SNPs associated with risk for breast cancer are shown in red, genes involved in the Notch signaling pathway are shown in blue and novel genes are shown in black.
Mentions: To further address the problem of reliability of GWAS data, we performed additional analyses combining genes containing SNPs replicated in multiple independent studies with genes involved in the Notch Signaling pathway. Genes containing SNPs reported in multiple independent studies included A2BP1, ADH1B, ALPL, ATM, BLM, CASP8, CCND1, CDKN1A, CHEK1, CSB, PMBT1, ECHDC1, EHMT, ERBB4, ESR1, FANCA, FGFR2, HCN1, ICAM5, IGF1, IGFIR, IGFBP3, KU80, LSP1, MGMT, MSH2, NEIL2, POLB, POLK, RAD51L1, RB1, RNF146, RPA1, RPA2, SKAP2, SOD2, MAP3K1, H19, TOX3, TGFB1, TNP1, XPA, XPC, XRCC3, XRCC4. The results are shown in Figure 7. We found that genes containing SNPs replicated in multiple independent studies interact with each other and with genes involved in the Notch signaling pathway, and genes involved in other breast cancer-relevant biological pathways. In addition, we identified novel genes not yet identified by GWAS (genes shown in black).

Bottom Line: However, they offer limited insights about the biological mechanisms by which SNPs confer risk.We then investigated their expression, along with 32 genes involved in the Notch signaling pathway using two publicly available gene expression data sets from the Caucasian (42 cases and 143 controls) and Asian (43 cases and 43 controls) populations.Pathway prediction and network modeling confirmed that Notch receptors and genes involved in the Notch signaling pathway interact with genes containing SNPs associated with risk for breast cancer.

View Article: PubMed Central - PubMed

Affiliation: Cancer Institute, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA.

ABSTRACT
Genome-wide association studies (GWAS) have identified SNPs associated with breast cancer. However, they offer limited insights about the biological mechanisms by which SNPs confer risk. We investigated the association of GWAS information with a major oncogenic pathway in breast cancer, the Notch signaling pathway. We first identified 385 SNPs and 150 genes associated with risk for breast cancer by mining data from 41 GWAS. We then investigated their expression, along with 32 genes involved in the Notch signaling pathway using two publicly available gene expression data sets from the Caucasian (42 cases and 143 controls) and Asian (43 cases and 43 controls) populations. Pathway prediction and network modeling confirmed that Notch receptors and genes involved in the Notch signaling pathway interact with genes containing SNPs associated with risk for breast cancer. Additionally, we identified other SNP-associated biological pathways relevant to breast cancer, including the P53, apoptosis and MAP kinase pathways.

No MeSH data available.


Related in: MedlinePlus