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A core MYC gene expression signature is prominent in basal-like breast cancer but only partially overlaps the core serum response.

Chandriani S, Frengen E, Cowling VH, Pendergrass SA, Perou CM, Whitfield ML, Cole MD - PLoS ONE (2009)

Bottom Line: In contrast, comparison to a panel of breast cancers revealed a strong concordance in gene expression between the Core MYC Signature and the basal-like breast tumor subtype, which is a subtype with poor prognosis.The Core MYC Signature has clinical relevance as this profile can be used to deduce an underlying genetic program that is likely to contribute to a clinical phenotype.Therefore, the presence of the Core MYC Signature may predict clinical responsiveness to therapeutics that are designed to disrupt MYC-mediated phenotypes.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology, Princeton University, Princeton, NJ, USA.

ABSTRACT

Background: The MYC oncogene contributes to induction and growth of many cancers but the full spectrum of the MYC transcriptional response remains unclear.

Methodology/principal findings: Using microarrays, we conducted a detailed kinetic study of genes that respond to MYCN or MYCNDeltaMBII induction in primary human fibroblasts. In parallel, we determined the response to steady state overexpression of MYCN and MYCNDeltaMBII in the same cell type. An overlapping set of 398 genes from the two protocols was designated a 'Core MYC Signature' and used for further analysis. Comparison of the Core MYC Signature to a published study of the genes induced by serum stimulation revealed that only 7.4% of the Core MYC Signature genes are in the Core Serum Response and display similar expression changes to both MYC and serum. Furthermore, more than 50% of the Core MYC Signature genes were not influenced by serum stimulation. In contrast, comparison to a panel of breast cancers revealed a strong concordance in gene expression between the Core MYC Signature and the basal-like breast tumor subtype, which is a subtype with poor prognosis. This concordance was supported by the higher average level of MYC expression in the same tumor samples.

Conclusions/significance: The Core MYC Signature has clinical relevance as this profile can be used to deduce an underlying genetic program that is likely to contribute to a clinical phenotype. Therefore, the presence of the Core MYC Signature may predict clinical responsiveness to therapeutics that are designed to disrupt MYC-mediated phenotypes.

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The Core MYC gene expression signature.Expression data for probes that are identified as responsive to both MYC-ER activation and steady state MYC overexpression are hierarchically clustered. The expression response of these probes is defined as the Core MYC signature. The signature probes total 428 Agilent probes that can be mapped to 385 unique unigene clusters.
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pone-0006693-g003: The Core MYC gene expression signature.Expression data for probes that are identified as responsive to both MYC-ER activation and steady state MYC overexpression are hierarchically clustered. The expression response of these probes is defined as the Core MYC signature. The signature probes total 428 Agilent probes that can be mapped to 385 unique unigene clusters.

Mentions: The two different data sets from induced and steady state MYCN overexpression suggest that the response to MYCN overexpression can be quite variable, depending on the method and timing of delivery. We reasoned that the genes common to the MYCN response in both experimental approaches would serve as a conservative estimate of a core ‘MYC gene expression signature’. Thus, we chose to focus on the genes responsive to MYCN overexpression in both experimental designs. Here forward we refer to this expression profile as the ‘Core MYC Signature’ (Figure 3).


A core MYC gene expression signature is prominent in basal-like breast cancer but only partially overlaps the core serum response.

Chandriani S, Frengen E, Cowling VH, Pendergrass SA, Perou CM, Whitfield ML, Cole MD - PLoS ONE (2009)

The Core MYC gene expression signature.Expression data for probes that are identified as responsive to both MYC-ER activation and steady state MYC overexpression are hierarchically clustered. The expression response of these probes is defined as the Core MYC signature. The signature probes total 428 Agilent probes that can be mapped to 385 unique unigene clusters.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2723908&req=5

pone-0006693-g003: The Core MYC gene expression signature.Expression data for probes that are identified as responsive to both MYC-ER activation and steady state MYC overexpression are hierarchically clustered. The expression response of these probes is defined as the Core MYC signature. The signature probes total 428 Agilent probes that can be mapped to 385 unique unigene clusters.
Mentions: The two different data sets from induced and steady state MYCN overexpression suggest that the response to MYCN overexpression can be quite variable, depending on the method and timing of delivery. We reasoned that the genes common to the MYCN response in both experimental approaches would serve as a conservative estimate of a core ‘MYC gene expression signature’. Thus, we chose to focus on the genes responsive to MYCN overexpression in both experimental designs. Here forward we refer to this expression profile as the ‘Core MYC Signature’ (Figure 3).

Bottom Line: In contrast, comparison to a panel of breast cancers revealed a strong concordance in gene expression between the Core MYC Signature and the basal-like breast tumor subtype, which is a subtype with poor prognosis.The Core MYC Signature has clinical relevance as this profile can be used to deduce an underlying genetic program that is likely to contribute to a clinical phenotype.Therefore, the presence of the Core MYC Signature may predict clinical responsiveness to therapeutics that are designed to disrupt MYC-mediated phenotypes.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology, Princeton University, Princeton, NJ, USA.

ABSTRACT

Background: The MYC oncogene contributes to induction and growth of many cancers but the full spectrum of the MYC transcriptional response remains unclear.

Methodology/principal findings: Using microarrays, we conducted a detailed kinetic study of genes that respond to MYCN or MYCNDeltaMBII induction in primary human fibroblasts. In parallel, we determined the response to steady state overexpression of MYCN and MYCNDeltaMBII in the same cell type. An overlapping set of 398 genes from the two protocols was designated a 'Core MYC Signature' and used for further analysis. Comparison of the Core MYC Signature to a published study of the genes induced by serum stimulation revealed that only 7.4% of the Core MYC Signature genes are in the Core Serum Response and display similar expression changes to both MYC and serum. Furthermore, more than 50% of the Core MYC Signature genes were not influenced by serum stimulation. In contrast, comparison to a panel of breast cancers revealed a strong concordance in gene expression between the Core MYC Signature and the basal-like breast tumor subtype, which is a subtype with poor prognosis. This concordance was supported by the higher average level of MYC expression in the same tumor samples.

Conclusions/significance: The Core MYC Signature has clinical relevance as this profile can be used to deduce an underlying genetic program that is likely to contribute to a clinical phenotype. Therefore, the presence of the Core MYC Signature may predict clinical responsiveness to therapeutics that are designed to disrupt MYC-mediated phenotypes.

Show MeSH
Related in: MedlinePlus