The frequency of B-other in different age groups of B-ALL and the genetic rearrangements characterizing the newly described UBTF/CDX2 ALL subtype. (A) An estimate of the fraction of B-ALL cases harboring a subtype-specific genetic alteration and those with an unknown genetic cause (B-other) when assessed by gold-standard methods or WGS and WTS. Gold-standard diagnostics typically include chromosome banding, fluorescence in situ hybridization (FISH), and targeted molecular tests. About 20% of the Philadelphia-like B-ALL subtype was estimated to be detectable indirectly by FISH. Frequency estimates were inferred from Gu et al and Kimura et al.^5,6 (B, left) The localization of the UBTF and ATXNL3 genes at 17q21 are schematically depicted. (right) A focal 10-kb genomic results in an in-frame UBTF::ATXN7L3 gene fusion at the breakpoint junction. (C, left) Schematic depiction of 13q12.2 in which the CDX2 gene is located ∼280 kb away from the active PAN3 gene enhancer. (right) A focal genomic deletion causes an aberrant chromatin looping configuration by which an active enhancer of the PAN3 gene is retargeted (“hijacked”) and starts driving the ectopic expression of the CDX2 gene. AYA, adolescents and young adults; HR, high risk; SR, standard risk.