Cryptic TCF3 fusions in childhood leukemia: Detection by RNA sequencing

Area of Science:

• Hematology
• Oncology
• Genetics

Background:

• Acute lymphoblastic leukemia (ALL) is a common childhood cancer with genetic markers identified in most cases.
• TCF3 gene fusions are present in 5%-11% of ALL patients, with varying prognostic implications.
• TCF3-HLF fusion indicates a poor prognosis, while TCF3-PBX1 is associated with a good prognosis.

Purpose of the Study:

• To evaluate targeted RNA sequencing for detecting TCF3 fusion genes in pediatric B-cell precursor ALL.
• To compare RNA sequencing with conventional cytogenetic and molecular methods for TCF3 fusion detection.
• To assess the clinical significance of different TCF3 fusion partners in ALL risk stratification.

Main Methods:

• Screening of 200 pediatric B-cell precursor ALL cases using targeted RNA sequencing.
• Comparison of RNA sequencing results with chromosome R-banding, fluorescence in situ hybridization, and PCR.
• Analysis of TCF3 fusion gene prevalence and types.

Main Results:

• TCF3 fusion genes were identified in 6.5% (13/200) of pediatric ALL patients.
• TCF3-PBX1 (5%), TCF3-FLI1 (1%), and TCF3-HLF (0.5%) fusions were detected.
• Discrepant results were observed between RNA sequencing and other methods, highlighting potential cryptic translocations.

Conclusions:

• Targeted RNA sequencing is a valuable tool for identifying TCF3 fusion genes in ALL.
• Accurate detection of TCF3 fusion partners is essential for precise risk assessment and treatment planning.
• Some TCF3 gene fusions may be cryptic and require advanced molecular techniques for detection.