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.


RESULTS
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
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.
Chandriani
Sanjay
S
Department of Molecular Biology, Princeton University, Princeton, NJ, USA.
Frengen
Eirik
E
Cowling
Victoria H
VH
Pendergrass
Sarah A
SA
Perou
Charles M
CM
Whitfield
Michael L
ML
Cole
Michael D
MD
D015153:Blotting, Western; D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling; D016259:Genes, myc; D006801:Humans; D007150:Immunohistochemistry; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis
Nat Rev Cancer. 2002 Oct;2(10):764-76
12360279
Genes Dev. 2000 Jun 1;14(11):1390-9
10837031
Science. 1999 Jan 1;283(5398):83-7
9872747
Cancer Cell. 2003 Sep;4(3):223-38
14522256
Development. 2003 Jan;130(1):15-28
12441288
Genes Dev. 2003 May 1;17(9):1115-29
12695333
Genes Dev. 2001 Jan 1;15(1):50-65
11156605
Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3260-5
10737792
Oncogene. 1999 May 13;18(19):3004-16
10378696
BMC Genomics. 2008 Sep 24;9:442
18816399
Bioinformatics. 2004 Jun 12;20(9):1453-4
14871861
PLoS Comput Biol. 2007 Apr 6;3(4):e63
17411336
Mol Cell Biol. 1987 May;7(5):1697-709
3299053
Cell. 1984 Dec;39(2 Pt 1):339-48
6498938
Proc Natl Acad Sci U S A. 2005 Mar 8;102(10):3738-43
15701700
Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8418-23
12829800
Mod Pathol. 2006 Feb;19(2):264-71
16341146
Cell. 2008 Mar 21;132(6):1049-61
18358816
EMBO Rep. 2003 May;4(5):484-90
12776737
Nature. 2002 Jan 31;415(6871):530-6
11823860
Science. 1996 Nov 29;274(5292):1523-7
8929412
Genes Dev. 1993 Apr;7(4):671-82
8458579
Bioinformatics. 2004 Dec 12;20(18):3710-5
15297299
Mol Cell Biol. 2002 Jul;22(14):5054-63
12077335
Cancer Cell. 2002 Jun;1(5):406-8
12124167
Nature. 2000 Aug 17;406(6797):747-52
10963602
J Biol Chem. 2003 Apr 4;278(14):12563-73
12529326
Oncogene. 2005 Jan 13;24(3):520-4
15516975
Nucleic Acids Res. 2004 Jun 29;32(11):3462-8
15226411
Nat Genet. 2006 Apr;38(4):421-30
16518402
Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9212-7
10430922
Genome Biol. 2003;4(10):R69
14519204
Nature. 1984 Aug 23-29;310(5979):655-60
6088986
Cancer Res. 2000 Nov 1;60(21):5922-8
11085504
Mol Cell Biol. 2006 Jun;26(11):4226-39
16705173
Nucleic Acids Res. 2001 Jan 15;29(2):397-406
11139609
Proc Natl Acad Sci U S A. 1986 Jul;83(13):4834-8
3014513
J Biol Chem. 2002 Oct 4;277(40):36921-30
12145275
Genes Dev. 1992 Dec;6(12A):2248-57
1459450
Clin Cancer Res. 2004 Jan 15;10(2):499-507
14760071
PLoS One. 2009;4(3):e4710
19270750
Nat Genet. 2005 Apr;37(4):382-90
15778709
Mol Cell. 2000 Feb;5(2):321-30
10882073
Cell. 1998 Aug 7;94(3):363-74
9708738
Oncogene. 2007 May 24;26(24):3582-6
17146437
Proc Natl Acad Sci U S A. 2006 Nov 21;103(47):17834-9
17093053
Nucleic Acids Res. 1995 May 25;23(10):1686-90
7784172
Mol Cell. 2003 May;11(5):1177-88
12769843
Mol Cell Biol. 1999 Jan;19(1):1-11
9858526
Cancer Cell. 2004 Dec;6(6):625-30
15607966
Proc Natl Acad Sci U S A. 2005 Sep 27;102(39):13968-73
16172399
Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5116-21
11309499
Cancer Cell. 2006 Dec;10(6):529-41
17157792
EMBO J. 2001 Mar 15;20(6):1383-93
11250904
N Engl J Med. 2002 Dec 19;347(25):1999-2009
12490681
Nat Rev Cancer. 2001 Oct;1(1):46-54
11900251
Proc Natl Acad Sci U S A. 2002 Apr 30;99(9):6274-9
11983916
Mol Cell. 2003 May;11(5):1189-200
12769844
Nucleic Acids Res. 2004 Oct 11;32(18):5368-78
15477387
PLoS One. 2008;3(12):e3932
19079543
Semin Cancer Biol. 2006 Aug;16(4):242-52
16935524
PLoS Biol. 2004 Feb;2(2):E7
14737219
BMC Genomics. 2006 Apr 27;7:96
16643655
Mol Cell Biol. 2005 May;25(9):3401-10
15831447
Cell. 1992 Apr 3;69(1):119-28
1555236
Nucleic Acids Res. 2003 Nov 1;31(21):6148-56
14576301