Until the year 2012, the key hallmarks of the genomic and transcriptional landscape of PCNSL—including frequent MYD88 and BCR mutations, chromosomal translocations, MHC deletions, aberrant SHM, patterns of genomic imbalances, and a GC exit profile—have been fully established by work carried out by us and others using hypothesis-driven targeted analyses (Figure 1 and Figure 2) [6,13,15,16,20,23,24,26,27,28,30,31,32,33,34,35,36,37]. The gene discussed is MYD88; the disease is primary central nervous system lymphoma.