Fig. 1: Single point mutation in NHR4 domain of Runx1t1 that abrogates neuroblastoma development.

a Kaplan–Meier survival analysis of progeny of the ENU-treated Th-MYCN mouse #1590, that were either wild-type for Runx1t1 (red, unsuppressed) or had inherited the Y534H Runx1t1 mutation (black, suppressed); n = 11 per genotype, p < 0.0001 (log-rank (Mantel–Cox) test). b Scatter plot showing time to tumor development in progeny of the ENU-treated mouse #1590 that were wild-type for Runx1t1 (red), or had inherited the Y534H mutation (black), n = 11 per genotype. c Multiple protein sequence alignment of the RUNX1T1 NHR4 domain across a range of organisms. The suppressed tumor phenotype resulted from the substitution of histidine (H) for a highly conserved tyrosine residue (Y), denoted by the asterisk (upper panel). A schematic model of wild-type and mutant Runx1t1 NHR4 zinc-finger motif domain folding (bottom panel). d Kaplan–Meier survival analysis for homozygous Th-MYCN mice either wild type (Th-MYCN +/+ Runx1t1 +/+) or with heterozygous knock-out (Th-MYCN +/+ Runx1t1 +/−) of Runx1t1. Wild-type Runx1t1 mice (red) demonstrated almost complete tumor penetrance, while Runx1t1 heterozygous knock-out mice (black) almost entirely lacked the ability to form tumors (n = 101 for wild-type and n = 163 for heterozygous knock-out, log-rank (Mantel–Cox) test p < 0.0001). Source data are provided as a Source Data file.