DNA sequence analysis of the major breakpoint cluster region of the BCR gene rearranged in Philadelphia-positive human leukemias.

ABSTRACT

We sought sequence characteristics that might explain the apparent high recombination frequency of the 5-kb BglII segment containing M-bcr exons 1, 2 and 3, and the intron to exon 4. An Alu sequence (subfamily Sx), in 5'-->3' orientation, lay in the middle of a 3-kb region that contains the great majority of Philadelphia chromosome breakpoint sites. The breakpoint of only one out of five chronic myeloid leukemia patients, for whom the BCR breakpoint site had been sequenced, was located within this Alu. Other features of interest for recombination were a 51-bp AT-rich region close to the 3' end, six hypervariable minisatellite consensus octamers, GC[A/T]GG[A/T]GG, six lymphoid recombinase heptamer signal sequences, one nonamer and a 16-bp inverted repeat. Dot matrix comparisons of the 5-kb M-bcr sequence with a 3-kb m-bcr2 segment showed significant homology only in corresponding Alu sequences.