Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Jung, MoonSun UNSPECIFIED UNSPECIFIED UNSPECIFIED Russell, Amanda J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Liu, Bing UNSPECIFIED UNSPECIFIED UNSPECIFIED George, Joshy UNSPECIFIED UNSPECIFIED UNSPECIFIED Liu, Pei Yan UNSPECIFIED UNSPECIFIED UNSPECIFIED Liu, Tao UNSPECIFIED orcid.org/0000-0001-6244-7316 UNSPECIFIED DeFazio, Anna UNSPECIFIED orcid.org/0000-0003-0057-4744 UNSPECIFIED Bowtell, David D. L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Oberthuer, Andre UNSPECIFIED UNSPECIFIED UNSPECIFIED London, Wendy B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Fletcher, Jamie I. UNSPECIFIED UNSPECIFIED UNSPECIFIED Haber, Michelle UNSPECIFIED orcid.org/0000-0003-2036-8817 UNSPECIFIED Norris, Murray D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Henderson, Michelle J. UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Keywords Language ONCOGENIC PATHWAY SIGNATURES; GENE-EXPRESSION SIGNATURE; BREAST-CANCER; C-MYC; SPONTANEOUS REGRESSION; MALIGNANT PROGRESSION; N-MYC; NEUROBLASTOMA; AMPLIFICATION; PROTEIN Multiple languages Oncology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/23973