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

Kerry E. Barber, Christine J. Harrison, Zoe J. Broadfield, Adam R.M. Stewart, Sarah L. Wright, Mary Martineau, Jon C. Strefford, Anthony Moorman

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)478-486
Number of pages9
JournalGenes Chromosomes and Cancer
Volume46
Issue number5
DOIs
StatePublished - May 1 2007
Externally publishedYes

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B-Lymphoid Precursor Cells
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Cytogenetics
Fluorescence In Situ Hybridization
Gene Fusion
Genes
Tumor Suppressor Genes
Chromosome Aberrations
Color

ASJC Scopus subject areas

  • Genetics
  • Cancer Research

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Molecular cytogenetic characterization of TCF3 (E2A)/19p13.3 rearrangements in B-cell precursor acute lymphoblastic leukemia. / Barber, Kerry E.; Harrison, Christine J.; Broadfield, Zoe J.; Stewart, Adam R.M.; Wright, Sarah L.; Martineau, Mary; Strefford, Jon C.; Moorman, Anthony.

In: Genes Chromosomes and Cancer, Vol. 46, No. 5, 01.05.2007, p. 478-486.

Research output: Contribution to journalArticle

Barber, KE, Harrison, CJ, Broadfield, ZJ, Stewart, ARM, Wright, SL, Martineau, M, Strefford, JC & Moorman, A 2007, 'Molecular cytogenetic characterization of TCF3 (E2A)/19p13.3 rearrangements in B-cell precursor acute lymphoblastic leukemia', Genes Chromosomes and Cancer, vol. 46, no. 5, pp. 478-486. https://doi.org/10.1002/gcc.20431
Barber, Kerry E. ; Harrison, Christine J. ; Broadfield, Zoe J. ; Stewart, Adam R.M. ; Wright, Sarah L. ; Martineau, Mary ; Strefford, Jon C. ; Moorman, Anthony. / Molecular cytogenetic characterization of TCF3 (E2A)/19p13.3 rearrangements in B-cell precursor acute lymphoblastic leukemia. In: Genes Chromosomes and Cancer. 2007 ; Vol. 46, No. 5. pp. 478-486.
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