• Cancer research · Feb 2017

    A Myc Activity Signature Predicts Poor Clinical Outcomes in Myc-Associated Cancers.

    • MoonSun Jung, Amanda J Russell, Bing Liu, Joshy George, Pei Yan Liu, Tao Liu, Anna DeFazio, David D L Bowtell, André Oberthuer, Wendy B London, Jamie I Fletcher, Michelle Haber, Murray D Norris, and Michelle J Henderson.
    • Children's Cancer Institute Australia, Lowy Cancer Research Centre, University of New South Wales Australia, Kensington, New South Wales, Australia.
    • Cancer Res. 2017 Feb 15; 77 (4): 971-981.

    AbstractMyc 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 Myc-driven tumors that might respond to Myc-targeted therapies. Cancer Res; 77(4); 971-81. ©2016 AACR.©2016 American Association for Cancer Research.

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