Jung, MoonSun, Russell, Amanda J., Liu, Bing, George, Joshy, Liu, Pei Yan, Liu, Tao ORCID: 0000-0001-6244-7316, DeFazio, Anna ORCID: 0000-0003-0057-4744, Bowtell, David D. L., Oberthuer, Andre, London, Wendy B., Fletcher, Jamie I., Haber, Michelle ORCID: 0000-0003-2036-8817, Norris, Murray D. and Henderson, Michelle J. (2017). A Myc Activity Signature Predicts Poor Clinical Outcomes in Myc-Associated Cancers. Cancer Res., 77 (4). S. 971 - 982. PHILADELPHIA: AMER ASSOC CANCER RESEARCH. ISSN 1538-7445

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Abstract

Myc transcriptional activity is frequently deregulated in human cancers, but a Myc-driven gene signature with prognostic ability across multiple tumor types remains lacking. Here, we selected 18 Myc-regulated genes from published studies of Myc family targets in epithelial ovarian cancer (EOC) and neuroblastoma. A Myc family activity score derived from the 18 genes was correlated to MYC/MYCN/MYCL1 expression in a panel of 35 cancer cell lines. The prognostic ability of this signature was evaluated in neuroblastoma, medulloblastoma, diffuse large B-cell lymphoma (DLBCL), and EOC microarray gene expression datasets using Kaplan-Meier and multivariate Cox regression analyses and was further validated in 42 primary neuroblastomas using qPCR. Cell lines with high MYC, MYCN, and/or MYCL1 gene expression exhibited elevated expression of the signature genes. Survival analysis showed that the signature was associated with poor outcome independently of well-defined prognostic factors in neuroblastoma, breast cancer, DLBCL, and medulloblastoma. In EOC, the 18-gene Myc activity signature was capable of identifying a group of patients with poor prognosis in a high-MYCN molecular subtype but not in the overall cohort. The predictive ability of this signature was reproduced using qPCR analysis of an independent cohort of neuroblastomas, including a subset of tumors without MYCN amplification. These data reveal an 18-gene Myc activity signature that is highly predictive of poor prognosis in diverse Myc-associated malignancies and suggest its potential clinical application in the identification of Mycdriven tumors that might respond to Myc-targeted therapies. (C)2016 AACR.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Jung, MoonSunUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Russell, Amanda J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Liu, BingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
George, JoshyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Liu, Pei YanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Liu, TaoUNSPECIFIEDorcid.org/0000-0001-6244-7316UNSPECIFIED
DeFazio, AnnaUNSPECIFIEDorcid.org/0000-0003-0057-4744UNSPECIFIED
Bowtell, David D. L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oberthuer, AndreUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
London, Wendy B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fletcher, Jamie I.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haber, MichelleUNSPECIFIEDorcid.org/0000-0003-2036-8817UNSPECIFIED
Norris, Murray D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Henderson, Michelle J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-239739
DOI: 10.1158/0008-5472.CAN-15-2906
Journal or Publication Title: Cancer Res.
Volume: 77
Number: 4
Page Range: S. 971 - 982
Date: 2017
Publisher: AMER ASSOC CANCER RESEARCH
Place of Publication: PHILADELPHIA
ISSN: 1538-7445
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
ONCOGENIC PATHWAY SIGNATURES; GENE-EXPRESSION SIGNATURE; BREAST-CANCER; C-MYC; SPONTANEOUS REGRESSION; MALIGNANT PROGRESSION; N-MYC; NEUROBLASTOMA; AMPLIFICATION; PROTEINMultiple languages
OncologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/23973

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