Molecular cytogenetic characterization of TCF3 (E2A)/19p13.3 rearrangements in B‐cell precursor acute lymphoblastic leukemia

KE Barber, CJ Harrison, ZJ Broadfield… - Genes …, 2007 - Wiley Online Library
KE Barber, CJ Harrison, ZJ Broadfield, ARM Stewart, SL Wright, M Martineau, JC Strefford
Genes, Chromosomes and Cancer, 2007Wiley Online Library
Abstract The t (1; 19)(q23; p13. 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‐PBX1 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 19p13 translocations, as well as an …
Abstract
The t(1;19)(q23;p13.3) is one of the most common chromosomal abnormalities in B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL) and usually gives rise to the TCF3PBX1 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 19p13 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” 19p13 translocations did not produce a split‐signal FISH pattern, a novel t(13;19)(q14;p13) involving TCF3 was discovered. A prospective screen of 161 children with BCP‐ALL revealed a cryptic t(12;19)(p13;p13), 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 19p13 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. © 2007 Wiley‐Liss, Inc.
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