Sensitivity of FISH in detection ofMLL translocations

Abstract

Fluorescence in situ hybridisation (FISH) detection of MLL translocations is now commonplace in cytogenetics laboratories. One of the most widely used probes is the Oncor MLL probe (Oncor, Gaithersburg, MD) that theoretically demonstrates the presence of an MLL rearrangement by a splitting of the FISH signal between the two derivative chromosomes generated by a translocation. Recently, another commercial probe has been made available from Vysis (Vysis, Downers Grove, IL) that uses a dual colour system. We examined material from 29 patients and 4 cell lines, all with recognised MLL translocations by G-banding, that were confirmed using Southern blot analysis of the MLL breakpoint cluster region. Both Oncor and Vysis MLL FISH probes were applied to these cases to compare their performance in detection of the MLL translocations. Thirty of the 33 cases demonstrated a clear splitting of Oncor MLL FISH signal in concordance with the Southern blot analysis and cytogenetics. Three cases failed to demonstrate a split MLL FISH signal. Therefore, we conclude that the Oncor MLL FISH probe has a 9.1% false negative rate, i.e., 90.9% sensitivity in detection of classic MLL translocations. Vysis MLL FISH detected the rearrangement in all 33 cases.