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

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 MYCNΔMBII induction in...

Descripción completa

Detalles Bibliográficos
Autores principales: Chandriani, Sanjay, Frengen, Eirik, Cowling, Victoria H., Pendergrass, Sarah A., Perou, Charles M., Whitfield, Michael L., Cole, Michael D.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2723908/
https://www.ncbi.nlm.nih.gov/pubmed/19690609
http://dx.doi.org/10.1371/journal.pone.0006693
_version_ 1782170376404467712
author Chandriani, Sanjay
Frengen, Eirik
Cowling, Victoria H.
Pendergrass, Sarah A.
Perou, Charles M.
Whitfield, Michael L.
Cole, Michael D.
author_facet Chandriani, Sanjay
Frengen, Eirik
Cowling, Victoria H.
Pendergrass, Sarah A.
Perou, Charles M.
Whitfield, Michael L.
Cole, Michael D.
author_sort Chandriani, Sanjay
collection PubMed
description 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 MYCNΔMBII induction in primary human fibroblasts. In parallel, we determined the response to steady state overexpression of MYCN and MYCNΔMBII 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.
format Text
id pubmed-2723908
institution National Center for Biotechnology Information
language English
publishDate 2009
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-27239082009-08-19 A Core MYC Gene Expression Signature Is Prominent in Basal-Like Breast Cancer but Only Partially Overlaps the Core Serum Response Chandriani, Sanjay Frengen, Eirik Cowling, Victoria H. Pendergrass, Sarah A. Perou, Charles M. Whitfield, Michael L. Cole, Michael D. PLoS One Research Article 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 MYCNΔMBII induction in primary human fibroblasts. In parallel, we determined the response to steady state overexpression of MYCN and MYCNΔMBII 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. Public Library of Science 2009-08-19 /pmc/articles/PMC2723908/ /pubmed/19690609 http://dx.doi.org/10.1371/journal.pone.0006693 Text en Chandriani et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Chandriani, Sanjay
Frengen, Eirik
Cowling, Victoria H.
Pendergrass, Sarah A.
Perou, Charles M.
Whitfield, Michael L.
Cole, Michael D.
A Core MYC Gene Expression Signature Is Prominent in Basal-Like Breast Cancer but Only Partially Overlaps the Core Serum Response
title A Core MYC Gene Expression Signature Is Prominent in Basal-Like Breast Cancer but Only Partially Overlaps the Core Serum Response
title_full A Core MYC Gene Expression Signature Is Prominent in Basal-Like Breast Cancer but Only Partially Overlaps the Core Serum Response
title_fullStr A Core MYC Gene Expression Signature Is Prominent in Basal-Like Breast Cancer but Only Partially Overlaps the Core Serum Response
title_full_unstemmed A Core MYC Gene Expression Signature Is Prominent in Basal-Like Breast Cancer but Only Partially Overlaps the Core Serum Response
title_short A Core MYC Gene Expression Signature Is Prominent in Basal-Like Breast Cancer but Only Partially Overlaps the Core Serum Response
title_sort core myc gene expression signature is prominent in basal-like breast cancer but only partially overlaps the core serum response
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2723908/
https://www.ncbi.nlm.nih.gov/pubmed/19690609
http://dx.doi.org/10.1371/journal.pone.0006693
work_keys_str_mv AT chandrianisanjay acoremycgeneexpressionsignatureisprominentinbasallikebreastcancerbutonlypartiallyoverlapsthecoreserumresponse
AT frengeneirik acoremycgeneexpressionsignatureisprominentinbasallikebreastcancerbutonlypartiallyoverlapsthecoreserumresponse
AT cowlingvictoriah acoremycgeneexpressionsignatureisprominentinbasallikebreastcancerbutonlypartiallyoverlapsthecoreserumresponse
AT pendergrasssaraha acoremycgeneexpressionsignatureisprominentinbasallikebreastcancerbutonlypartiallyoverlapsthecoreserumresponse
AT peroucharlesm acoremycgeneexpressionsignatureisprominentinbasallikebreastcancerbutonlypartiallyoverlapsthecoreserumresponse
AT whitfieldmichaell acoremycgeneexpressionsignatureisprominentinbasallikebreastcancerbutonlypartiallyoverlapsthecoreserumresponse
AT colemichaeld acoremycgeneexpressionsignatureisprominentinbasallikebreastcancerbutonlypartiallyoverlapsthecoreserumresponse
AT chandrianisanjay coremycgeneexpressionsignatureisprominentinbasallikebreastcancerbutonlypartiallyoverlapsthecoreserumresponse
AT frengeneirik coremycgeneexpressionsignatureisprominentinbasallikebreastcancerbutonlypartiallyoverlapsthecoreserumresponse
AT cowlingvictoriah coremycgeneexpressionsignatureisprominentinbasallikebreastcancerbutonlypartiallyoverlapsthecoreserumresponse
AT pendergrasssaraha coremycgeneexpressionsignatureisprominentinbasallikebreastcancerbutonlypartiallyoverlapsthecoreserumresponse
AT peroucharlesm coremycgeneexpressionsignatureisprominentinbasallikebreastcancerbutonlypartiallyoverlapsthecoreserumresponse
AT whitfieldmichaell coremycgeneexpressionsignatureisprominentinbasallikebreastcancerbutonlypartiallyoverlapsthecoreserumresponse
AT colemichaeld coremycgeneexpressionsignatureisprominentinbasallikebreastcancerbutonlypartiallyoverlapsthecoreserumresponse