The value of interphase fluorescence in situ hybridization for the detection of translocation t(12;21) in childhood acute lymphoblastic leukemia

Translocation t(12;21)(p13;q22) is the most frequent cytogenetic abnormalit y in childhood acute lymphoblastic leukemia (ALL) and is generally associat ed with favorable prognosis. In this report, we assessed the value of dual- color interphase fluorescence in situ hybridization (FISH) for the detectio n of t(12;21). Fifty-three patients were screened for ETV6/CBFA2 fusion by means of FISH, using two cosmid probes mapped on ETV6 and on CBFA2, respect ively. The cut-off value (mean + three standard deviations) for positivity established on control patients was 9.3%. A comparison between FISH and mol ecular methods [reverse-transcriptase polymerase chain reaction/Southern bl ot (RT-PCR/SB)] was possible in 52 patients: 34 of 52 (65.4%) showed negati ve results with both approaches, and 13 of 52 (25%) were positive; 5 of 52 (9.6%) showed discrepancies: four patients who were positive using RT-PCR/S B were negative using FISH. Conversely, one patient negative when using RT- PCR/SB was positive with FISH. Further investigations on this patient, cyto genetically characterized by add(lap), showed an atypical breakpoint on ETV 6, located 5' to the common breakpoint. Compared with RT-PCR and SE, dual-c olor interphase FISH with the cosmid probe set proved to be highly specific but showed limited sensitivity.