Genomic acute myeloid leukemia-associated inv(16)(p13q22) breakpoints are tightly clustered

The inv(16) and related t(16;16) are found in 10% of all cases with ne novo acute myeloid leukemia. In these rearrangements the core binding factor be ta (CBFB) gene on 16q22 is fused to the smooth muscle myosin heavy chain ge ne (MYH11) on 16p13, To gain insight into the mechanisms causing the inv(16 ) ne have analysed 24 genomic CBFB-MYH11 breakpoints. All breakpoints in CB FB are located in a 15-Kb intron, More than 50% of the sequenced 6.2 Kb of this intron consists of human repetitive elements. Twenty-one of the 24 bre akpoints in MYH11 are located in a 370-hp intron, The remaining three break points in MYH11 ape located more upstream, The localization of three breakp oints adjacent to a V(D)J recombinase signal sequence in MYH11 suggests a V (D)J recombinase-mediated rearrangement in these cases, V(D)J recombinase-a ssociated characteristics (small nucleotide deletions and insertions of ran dom nucleotides) were detected in six other cases. CBFB and MYH11 duplicati ons were detected in four of six cases tested.