As the KMT2A expression and MYC activity relationship become inverted upon progression to metastatic disease, the tight association with AR and HOXB13 lineage-specific drivers is presumably lost, suggesting a context-dependent role for KMT2A in PCa with increased MYC activity; increased KMT2A expression (and likely its activity) may drive development of primary disease but not advanced PCa. Here, HOXB13 is linked to posterior cortical atrophy.