A Core MYC Gene Expression Signature is Prominent in Basal-like Breast Cancer but Only Partially Overlaps the Core Serum Response

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2009 Aug 20

PMID 19690609

Citations 93

Authors

Sanjay Chandriani

Eirik Frengen

Victoria H Cowling

Sarah A Pendergrass

Charles M Perou

Michael L Whitfield

Michael D Cole

Affiliations

Soon will be listed here.

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.

Citing Articles

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Ohara Y, Tang W, Liu H, Yang S, Dorsey T, Cawley H Cell Rep. 2023; 42(12):113434.

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Vitamin B supports MYC oncogenic metabolism and tumor progression in breast cancer.

Kreuzaler P, Inglese P, Ghanate A, Gjelaj E, Wu V, Panina Y Nat Metab. 2023; 5(11):1870-1886.

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