Cryptic TCF3 fusions in childhood leukemia: Detection by RNA sequencing.
Basic Helix-Loop-Helix Transcription Factors
/ genetics
Child
Chromosome Banding
Humans
In Situ Hybridization, Fluorescence
Oncogene Proteins, Fusion
/ genetics
Pilot Projects
Polymerase Chain Reaction
Precursor Cell Lymphoblastic Leukemia-Lymphoma
/ genetics
Prognosis
Proto-Oncogene Protein c-fli-1
/ genetics
Sequence Analysis, RNA
Translocation, Genetic
RNA sequencing
TCF3
acute lymphoblastic leukemia
cytogenetics
Journal
Genes, chromosomes & cancer
ISSN: 1098-2264
Titre abrégé: Genes Chromosomes Cancer
Pays: United States
ID NLM: 9007329
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
revised:
27
08
2021
received:
27
05
2021
accepted:
27
08
2021
pubmed:
31
8
2021
medline:
19
3
2022
entrez:
30
8
2021
Statut:
ppublish
Résumé
Acute lymphoblastic leukemia (ALL) is the most frequent malignancy in childhood and adolescence. In more than 60% of cases of this heterogeneous disease, a genetic marker is identified via cytogenetic or molecular analyses. TCF3 gene fusions occur in 5%-11% of ALL patients. In < 1%, the TCF3 alteration in ALL leads to a TCF3-HLF fusion gene. Even though this is a very rare event, the detection of a TCF3-HLF fusion gene is associated with a very poor prognosis with incurable relapses in almost all patients. The frequent TCF3-PBX1 fusion gene, which is detectable in 5%-10% of childhood B-cell precursor ALLs and ~3.8% of adult B-cell precursor ALLs, is associated with a rather good prognosis, that is, an observed event-free 5-year survival of approximately 85%. Thus, the distinction of the different partner genes fused to TCF3 is essential for risk assessment. To verify RNA sequencing as a tool for detection of known and unknown fusion genes, we screened 200 cases of pediatric B-cell precursor ALL with "targeted" RNA sequencing in a pilot project in comparison to classical cytogenetic analyses (chromosome R-banding analysis), fluorescence in situ hybridization, and PCR. We observed a TCF3 fusion gene in 6.5% (13/200) of the patients. Ten (5%) patients displayed a TCF3-PBX1 fusion gene, two (1%) patients a TCF3-FLI1 fusion gene, and one (0.5%) patient a TCF3-HLF fusion gene. For the TCF3 fusions, we obtained discrepant results with the different methods, which are described in the article. Taken together, translocations leading to TCF3 fusion genes might appear cryptic and may remain undetected by a single method.
Substances chimiques
Basic Helix-Loop-Helix Transcription Factors
0
FLI1 protein, human
0
Oncogene Proteins, Fusion
0
Proto-Oncogene Protein c-fli-1
0
TCF3 protein, human
0
TCF3-HLF fusion protein, human
0
TCF3-PBX1 fusion protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
22-26Informations de copyright
© 2021 The Authors. Genes, Chromosomes and Cancer published by Wiley Periodicals LLC.
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