title: Molecular characterization of a rare MLL-AF4 (MLL-AFF1) fusion rearrangement in infant leukemia.
abstract: The t(4;11)(q21;q23) involving the genes MLL and AF4 (alias for AFF1) is detected in 50-70% of infant leukemia. We characterize at both the DNA and RNA level a rare MLL-AF4 fusion transcript identified in a 15-month-old girl with acute lymphoblastic leukemia. Direct sequence analysis of the reverse transcriptase-polymerase chain reaction product showed an in-frame fusion between MLL exon 9 and AF4 exon 6. We further demonstrated that the genomic breakpoints were located 1,553 bp downstream of MLL exon 9 and 1,239 bp upstream of AF4 exon 6. Four Alu repeats were detected in MLL intron 9 and two Alu repeats and one LINE1 repetitive element were identified downstream of AF4 exon 5. Finally, a 9-bp polypurine (A) tract and an 8-bp polypyrimidine (T) tract were found flanking the translocation breakpoint. In summary, we have characterized at both the RNA and the DNA level a rare MLL-AF4 fusion variant that was presumably mediated by Alu repeats or polypurine and polypyrimidine tracts located in the vicinity of genomic breakpoints.
authors: Department of Genetics, Portuguese Oncology Institute, Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal.
authors: Susana
authors: S
authors: Bizarro
authors: Nuno
authors: N
authors: Cerveira
authors: Cecília
authors: C
authors: Correia
authors: Susana
authors: S
authors: Lisboa
authors: Ana
authors: A
authors: Peixoto
authors: Lucília
authors: L
authors: Norton
authors: Manuel R
authors: MR
authors: Teixeira
mesh_terms: D001483:Base Sequence; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology*; D005091:Exons; D005260:Female; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007223:Infant; D007938:Leukemia / Q000235:genetics*; D008969:Molecular Sequence Data; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics* / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics* / Q000502:physiology*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011687:Purines / Q000737:chemistry; D011743:Pyrimidines / Q000737:chemistry; D012313:RNA / Q000378:metabolism; D017422:Sequence Analysis, DNA; D035602:Transcriptional Elongation Factors
chemical_list: D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D011687:Purines; D011743:Pyrimidines; D035602:Transcriptional Elongation Factors; D051788:Myeloid-Lymphoid Leukemia Protein; C081449:AFF1 protein, human; D012313:RNA; D004247:DNA; D011495:Histone-Lysine N-Methyltransferase