title: Molecular cytogenetic characterization of TCF3 (E2A)/19p13.3 rearrangements in B-cell precursor acute lymphoblastic leukemia.
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 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.
authors.affiliation: Leukaemia Research Cytogenetics Group, Cancer Sciences Division, University of Southampton, Southampton, UK.
authors.forename: Kerry E
authors.initials: KE
authors.lastname: Barber
authors.forename: Christine J
authors.initials: CJ
authors.lastname: Harrison
authors.forename: Zoe J
authors.initials: ZJ
authors.lastname: Broadfield
authors.forename: Adam R M
authors.initials: AR
authors.lastname: Stewart
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Wright
authors.forename: Mary
authors.initials: M
authors.lastname: Martineau
authors.forename: Jon C
authors.initials: JC
authors.lastname: Strefford
authors.forename: Anthony V
authors.initials: AV
authors.lastname: Moorman
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D002051:Burkitt Lymphoma / Q000235:genetics* / Q000473:pathology; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D002888:Chromosomes, Human, Pair 19; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007399:Interphase; D007621:Karyotyping; D011230:Precancerous Conditions / Q000235:genetics / Q000473:pathology; D017384:Sequence Deletion; D014178:Translocation, Genetic
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; C407909:TCF3 protein, human