Molecular cytogenetic characterization of TCF3 (E2A)/19p 13.3 rearrangements in B-cell precursor acute lymphoblastic leukemia

The t(1; 19)(q23;p 13.3) is one of the most common chromosomal abnormalities in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) and usually gives rise to the TCF3-PBXI fusion gene. Additional rare, and sometimes cytogenetically cryptic, translocations involving the TCF3 gene have also been described. Using a dual color split-signal fluorescence in situ hybridization (FISH) probe, we have investigated the involvement of this gene in a series of BCP-ALLs harboring 19p 13 translocations, as well as an unselected patient cohort. The TCF3 gene was shown to be involved in the majority of cases with a cytogenetically visible t(1; 19) translocation, while the remaining TCF3-negative ALLs demonstrated breakpoint heterogeneity. Although most "other" 19p 13 translocations did not produce a split-signal FISH pattern, a novel t(13; 1 9)(q 14;p 13) involving TCF3 was discovered. A prospective screen of 161 children with BCP-ALL revealed a cryptic t(12; 19)(p13;p 13), another novel TCF3 rearrangement, and a series of patients with submicroscopic deletions of TCF3. These results demonstrate the utility of a split-signal FISH strategy in confirming the involvement of the TCF3 gene in 19p 13 rearrangements and in identifying novel and cryptic TCF3 translocations. In addition to its role as a fusion partner gene, we propose that TCF3 can also act as a tumor suppressor gene in BCP-ALL. (c) 2007 Wiley-Liss, Inc.