Comprehensive characterization of a novel intronic pseudo-exon inserted within an e14/a2 BCR-ABL rearrangement in a patient with chronic myeloid leukemia.
We identified a novel breakpoint cluster region-ABL rearrangement in a chronic myeloid leukemia (CML) patient. The e14/a2 (b3/a2) type BCR-ABL mRNA incorporated a 42-nucleotide intronic insertion of ABL intron Ib between BCR exon e14 and ABL exon a2. As we hypothesized that the rearrangement between BCR and ABL genes occurred near the inserted sequence and because of the relative small size of BCR intron 14, we determined the BCR-ABL breakpoint at the genomic DNA level. Using a PCR-based method, this analysis revealed that i) BCR intron 14 brought a potential lariat branch point and the polypyrimidine tract, ii) the BCR-ABL breakpoint created a chimeric acceptor site, and iii) the inserted sequence of ABL intron Ib carried at its 3' end a well-conserved donor splice site. Therefore, the inserted sequence was flanked by canonical consensus splice sites and recognized as a pseudo-exon (as shown by splice site prediction and exon finder software). Moreover, the insertion did not disrupt the reading frame between BCR and ABL and did not produce a premature stop codon. Instead, this novel BCR-ABL chimeric transcript encoded a functional oncoprotein with an in-frame insertion of 15 new amino acids.
Service d'Hématologie et Oncologie Biologique - INSERM U935, Centre Hospitalier Universitaire de Poitiers, 2, rue de la Milétrie, 86021 Poitiers Cedex, France.
Nathalie
N
Sorel
Caroline
C
Mayeur-Rousse
Séverine
S
Deverrière
Lydia
L
Roy
Elisabeth
E
Brottier-Mancini
François
F
Guilhot
Ali G
AG
Turhan
Jean Claude
JC
Chomel
D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D019457:Chromosome Breakage; D016384:Consensus Sequence / Q000235:genetics; D005091:Exons / Q000235:genetics*; D016044:Fusion Proteins, bcr-abl / Q000737:chemistry / Q000235:genetics*; D015321:Gene Rearrangement / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional / Q000235:genetics*; D022821:RNA Splice Sites / Q000235:genetics
D022821:RNA Splice Sites; D016044:Fusion Proteins, bcr-abl