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DOI: 10.1055/s-0029-1222654
Identification of first and second genomic lesions in ETV6-RUNX1 positive childhood acute lymphoblastic leukaemia (ALL)
Background: The ETV6-RUNX1 translocation, resulting from t(12;21)(p13;q22), is the most common chromosomal translocation in childhood ALL. The genomic ETV6-RUNX1 fusion site is unique to individual patients and represents an ideal molecular marker for absolute quantification. This chromosomal translocation (“first-hit“) alone is insufficient to induce leukemia, additional secondary genetic events (“second-hit“) are necessary.
Patients and method: ETV6-RUNX1 fusion sites were amplified from bone marrow DNA of 65 pediatric ALL patients using a two-round multiplex long-range PCR (MLR-PCR). Secondary genetic aberrations were analysed by high-resolution microarrays.
Results: MLR-PCR successfully amplified patient-specific fusion sites in 60 of 65 tested DNA. Secondary genetic abberrations identified by microarrays were used as markers to study the clonal evolution of malignant cells.
Conclusion: In addition to quantification of minimal residual disease using the genomic ETV6-RUNX1 fusion site, clone specific sequences derived from secondary mutations allow monitoring of malignant cell clones during therapeutic intervention and relapse.