Determination Of The Origin Of The T(1;19) Tcf3-Pbx1 Fusion By Genomic Inverse Pcr For Exploration Of Ligated Breakpoints (Gipfel)

Pediatric acute lymphoblastic leukemia (ALL) is characterized by recurrent chromosomal translocations. The translocation t(1;19) that fuses the gene encoding the basic helix-loop-helix transcription factor TCF3 with the gene encoding the homeodomain protein PBX1 is the second most common one occurring in approximately 5-10% of precursor B ALL cases. Backtracking of clonotypic TCF3-PBX1 translocations that were identified in leukemia patients by PCR amplification of Guthrie cards from these individuals provided weak evidence for a prenatal origin of a minority of TCF3-PBX1 translocations (2 of 15 cases). The presence of N-nucleotides at the recombination junction, IGH rearrangements and the specific JH and DH segment usage indirectly supported a postnatal origin of the majority of translocations, but could not definitely date the fusion event during development (Wiemels et al. PNAS 2002).