Characterization of TCF3 rearrangements in pediatric B-lymphoblastic leukemia/lymphoma by mate-pair sequencing (MPseq) identifies complex genomic rearrangements and a novel TCF3/TEF gene fusion

Ross A. Rowsey, Stephanie A. Smoley, Cynthia M. Williamson, George Vasmatzis, James B. Smadbeck, Yi Ning, Patricia T. Greipp, Nicole L. Hoppman, Linda B. Baughn, Rhett P. Ketterling, Jess F. Peterson

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Abstract

The TCF3/PBX1 gene fusion is a recurrent genetic abnormality in pediatric B-lymphoblastic leukemia/lymphoma (B-ALL/LBL). While dual-color, dual-fusion fluorescence in situ hybridization (D-FISH) probes can detect TCF3/PBX1 fusions, further characterization of atypical TCF3 FISH patterns as indicated by additional or diminished TCF3 signals is currently limited. Herein we describe the use of a next-generation sequencing assay, mate-pair sequencing (MPseq), to characterize typical and cryptic TCF3/PBX1 fusions and to identify TCF3 translocation partners based on results obtained from our laboratory-developed TCF3/PBX1 D-FISH probe set. MPseq was performed on 21 cases of pediatric B-ALL/LBL with either TCF3/PBX1 fusion, or no TCF3/PBX1 fusion but with additional or diminished TCF3 signals obtained by our PBX1/TCF3 D-FISH probe set. In addition, MPseq was performed on one pediatric B-ALL/LBL case with an apparently normal karyotype and abnormal TCF3 break-apart probe results. Of 22 specimens successfully evaluated by MPseq, 13 cases (59%) demonstrated TCF3/PBX1 fusion, including three cases with previously undescribed insertional rearrangements. The remaining nine cases (41%) harbored various TCF3 partners, including six cases with TCF3/ZNF384, and one case each with TCF3/HLF, TCF3/FLI1 and TCF3/TEF. Our results illustrate the power of MPseq to characterize TCF3 rearrangements with increased precision and accuracy over traditional cytogenetic methodologies.

Original languageEnglish (US)
Article number81
JournalBlood cancer journal
Volume9
Issue number10
DOIs
StatePublished - Oct 1 2019

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Gene Fusion
Fluorescence In Situ Hybridization
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Pediatrics
Abnormal Karyotype
Cytogenetics
Color

ASJC Scopus subject areas

  • Hematology
  • Oncology

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Characterization of TCF3 rearrangements in pediatric B-lymphoblastic leukemia/lymphoma by mate-pair sequencing (MPseq) identifies complex genomic rearrangements and a novel TCF3/TEF gene fusion. / Rowsey, Ross A.; Smoley, Stephanie A.; Williamson, Cynthia M.; Vasmatzis, George; Smadbeck, James B.; Ning, Yi; Greipp, Patricia T.; Hoppman, Nicole L.; Baughn, Linda B.; Ketterling, Rhett P.; Peterson, Jess F.

In: Blood cancer journal, Vol. 9, No. 10, 81, 01.10.2019.

Research output: Contribution to journalArticle

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abstract = "The TCF3/PBX1 gene fusion is a recurrent genetic abnormality in pediatric B-lymphoblastic leukemia/lymphoma (B-ALL/LBL). While dual-color, dual-fusion fluorescence in situ hybridization (D-FISH) probes can detect TCF3/PBX1 fusions, further characterization of atypical TCF3 FISH patterns as indicated by additional or diminished TCF3 signals is currently limited. Herein we describe the use of a next-generation sequencing assay, mate-pair sequencing (MPseq), to characterize typical and cryptic TCF3/PBX1 fusions and to identify TCF3 translocation partners based on results obtained from our laboratory-developed TCF3/PBX1 D-FISH probe set. MPseq was performed on 21 cases of pediatric B-ALL/LBL with either TCF3/PBX1 fusion, or no TCF3/PBX1 fusion but with additional or diminished TCF3 signals obtained by our PBX1/TCF3 D-FISH probe set. In addition, MPseq was performed on one pediatric B-ALL/LBL case with an apparently normal karyotype and abnormal TCF3 break-apart probe results. Of 22 specimens successfully evaluated by MPseq, 13 cases (59{\%}) demonstrated TCF3/PBX1 fusion, including three cases with previously undescribed insertional rearrangements. The remaining nine cases (41{\%}) harbored various TCF3 partners, including six cases with TCF3/ZNF384, and one case each with TCF3/HLF, TCF3/FLI1 and TCF3/TEF. Our results illustrate the power of MPseq to characterize TCF3 rearrangements with increased precision and accuracy over traditional cytogenetic methodologies.",
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AU - Williamson, Cynthia M.

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AU - Smadbeck, James B.

AU - Ning, Yi

AU - Greipp, Patricia T.

AU - Hoppman, Nicole L.

AU - Baughn, Linda B.

AU - Ketterling, Rhett P.

AU - Peterson, Jess F.

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