Abstract PR09: MYCN and is a therapeutic target in neuroblastoma

Neuroblastoma is a childhood cancer of the sympathetic nervous system. Approximately 20% of patients present with an aggressive metastatic disease characterized by amplification of the MYCN locus. However, an additional 30% of patients suffer from an equally aggressive disease, yet there are no unified genetic markers available.To identify potential biomarkers of poor prognosis in neuroblastoma, we conducted unsupervised hierarchical clustering on 649 primary neuroblastoma tumors based on a 51 gene MYC core target signature. This demonstrated strong activation within the MYCN amplified cohort as expected, but surprisingly there was a large subset of MYCN non-amplified patients that exhibited high MYC signaling. High expression of this MYC signature proved to be strongly predictive of poor overall survival, in both the full cohort (Hazard ratio (HR): 47.6, p= 2.7x10-35, n=649) and in MYCN non-amplified patients (HR=32.8, p=1.3x10-13, n=554), suggesting that neuroblastoma can be driven by MYC signaling in the absence of MYCN amplification. To evaluate potential therapeutic targets within this MYC signature, we conducted cox regression analysis on the 51 individual members and identified that SPT16 was a particularly potent predictor of poor outcome in these 649 neuroblastoma patients (HR: 7.2, p=2.7x10-17). SPT16 is a subunit of the FACT histone chaperone complex, which together with its heterodimer partner SSRP1, has previously been shown to function in dynamic regulation of c...

Source: Molecular Cancer Research - October 18, 2015 Category: Cancer & Oncology Authors: Carter, D. R., Murray, J., Cheung, B. B., Kalla, H., Gamble, L., Tsang, J., Sutton, S., Koach, J., Syed, S., Gifford, A., Issaeva, N., Biktasova, A., Atmadibrata, B., Sun, Y., Sokolowski, N., Ling, D., Kim, P. Y., Webber, H., Clark, A., Ruhle, M., Liu, B. Tags: Targeting Myc-Driven Cancers: Oral Presentations - Proffered Abstracts Source Type: research