An 18-gene Myc activity signature for neuroblastoma and other Myc-driven cancers — ASN Events
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  2. Afternoon Tea/Poster Session
  3. An 18-gene Myc activity signature for neuroblastoma and other Myc-driven cancers

An 18-gene Myc activity signature for neuroblastoma and other Myc-driven cancers (#124)

MoonSun Jung 1 , Amanda Russell 1 , Anna DeFazio 2 , Joshy George 3 , David D.L. Bowtell 3 , Bing Liu 1 , Andre Oberthuer 4 , Wendy B. London 5 , Michelle Haber 1 , Murray D. Norris 1 , Michelle J. Henderson 1
  1. Children's Cancer Institute Australia, Sydney, NSW, Australia
  2. Department of Gynaecological oncology and Westmead Institute for Cancer research, University of Sydney at the Westmead Millennium Institute, Sydney, NSW, Australia
  3. Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
  4. Children’s Hospital, Department of Pediatric Oncology and Hematology, University of Cologne and Centre for Molecular Medicine Cologne, Cologne, Germany
  5. Children’s Oncology Group Statistics and Data Center and Boston Children’s Hospital/Dana-Farber Cancer Institute, Boston, MA, USA

Purpose
Deregulation of the Myc transcription factor family and its downstream targets plays a crucial role in human cancers. Expression profiling studies have identified prognostic Myc-regulated gene-sets for several cancers, however the generation of a succinct Myc activity signature for risk-stratification in multiple cancer types would facilitate development of novel targeted therapies for Myc-driven cancers.   

Experimental Design
18 genes were selected from published Myc-regulated gene lists based on a priori biological knowledge and on analysis of neuroblastoma and epithelial ovarian cancer (EOC) microarray datasets. Signature scores were determined using real-time PCR (qPCR) and Taqman-low-density arrays for a panel of 35 cancer cell lines and 42 primary neuroblastomas. The prognostic value of the 18-gene Myc activity signature was analysed in neuroblastoma, medulloblastoma, diffuse large B-cell lymphoma (DLBCL) and EOC microarray datasets using Kaplan-Meier analysis.

Results
In cancer cell lines, the signature score positively correlated with overall MYC/MYCN/MYCL1 expression. Microarray dataset analysis showed that a high score was predictive of poor outcome independently of MYCN amplification (P<0.001) in neuroblastoma, but not in the overall cohort of EOC. However, a high score conferred a poor prognosis in specific EOC molecular subtypes and in other Myc-driven cancers including medulloblastoma (P=0.012), DLBCL (P=0.019), and breast cancer (P=0.019). The prognostic performance of the signature remained significant in both overall and non-MYCN amplified neuroblastoma, when evaluated with qPCR.

Conclusion
This study identified an 18-gene signature reflecting Myc transcriptional activity and carrying prognostic power across multiple Myc-driven cancers. Use of the signature in different platforms confirmed its robustness, and suggests its clinical applicability for identifying targeted therapies.