Extended Data Fig. 1: Metabolomic profiling of MYCN-amplified primary patient tumors and xenografts reveals reprogramming of the arginine-proline-glutamine axis.
From: Reprogramming neuroblastoma by diet-enhanced polyamine depletion
a) Global metabolomic signatures of primary human neuroblastoma tumors analyzed by principal component analysis, with MYCN-amplified (red) and non-amplified (blue). b) Heatmap of significantly changed metabolites in primary neuroblastoma tumor samples (q < 0.05), comparing MYCN-amplified to non-amplified tumors. Unsupervised clustering performed using Ward’s method. c) Levels of all proteinogenic amino acids in primary neuroblastoma tumor tissue. Data in a-c as in Fig. 1b with n = 10 each group and p-values corrected for false discovery rate.*q < 0.05. Mean ± s.e.m. d) Relative levels of polyamine related metabolites in bilateral xenografts from respective MYCN-amplified and non-amplified neuroblastoma cell lines. *P < 0.05, **P < 0.01, two-tailed paired t-test. Mean ± s.e.m., n = 4. e) Proline concentration in MYCN-driven neuroblastoma tumors is significantly increased in the Th-MYCN mouse model, whereas glutamine, arginine, ornithine and glutamate levels across organs are within physiological range. d,e, Mean ± s.e.m., proline tumor n = 31 other organs n = 8-31, glutamine tumor n = 29 other organs n = 8-29, arginine tumor n = 25 other organs n = 8-25 and tumor ornithine n = 24; glutamate tumor n = 23 other organs n = 8-25. f) Relative metabolite levels across tumors harvested at early (< 50 mm3) compared to the late timepoint in the Th-MYCN model. **P < 0.01, ***P < 0.001, Two-tailed t-test. Mean ± s.e.m., early n = 10, late n = 14. Panels d and e created in BioRender. Noureddine, N. (2025) https://BioRender.com/vxtxvhq.
