Molecular characterization of a new recombination of the SIL/TAL-1 locus in a child with T-cell acute lymphoblastic leukaemia

Br J Haematol. 2002 Sep;118(4):1011-8. doi: 10.1046/j.1365-2141.2002.03747.x.

Abstract

Deletions involving the SIL-TAL-1 locus are seen in 15% of T-acute lymphoblastic leukaemias (T-ALL). To date, seven deletions have been described, spreading over 90 kb of chromosome 1, fusing SIL to the TAL-1 gene and resulting in over expression of TAL-1. During the diagnostic screening of the TAL-1 deletion in 176 T-ALL patients, we identified one case showing a new SIL rearrangement. A novel fusion transcript was identified between the SIL exon 1a and an unknown sequence (633-cDNA). Polymerase chain reaction (PCR) screening of a human cDNA library confirmed the existence of this transcript. Using long-distance PCR on patient DNA, we obtained a genomic fragment containing SIL exon 1b, a portion of intron 1b, an unknown sequence and the 633 sequence. Using DNA from healthy donors, a partial genomic map of 633-DNA was found to be identical to the restriction map of the PCR fragment amplified from patient DNA. To define the chromosomal origin of 633-DNA, a YAC human genomic library was screened. Two clones containing 633-DNA were found, mapping to chromosomal region 1p32 and both contained SIL and TAL-1 sequences. By searching GenBank, we identified PAC RP1-18D14 which contains SIL, TAL-1 and 633-DNA, confirming this novel rearrangement as a new deletion of the SIL/TAL-1 locus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Basic Helix-Loop-Helix Transcription Factors
  • Blotting, Southern / methods
  • Child
  • Child, Preschool
  • Chromosome Mapping
  • Chromosomes, Human, Pair 1
  • DNA-Binding Proteins / genetics*
  • Gene Deletion*
  • Gene Rearrangement*
  • Humans
  • Infant
  • Intracellular Signaling Peptides and Proteins
  • Leukemia-Lymphoma, Adult T-Cell / genetics*
  • Oncogene Proteins, Fusion*
  • Polymerase Chain Reaction / methods
  • Proteins / genetics
  • Proto-Oncogene Proteins / genetics*
  • T-Cell Acute Lymphocytic Leukemia Protein 1
  • Transcription Factors / genetics*

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • Intracellular Signaling Peptides and Proteins
  • Oncogene Proteins, Fusion
  • Proteins
  • Proto-Oncogene Proteins
  • STIL protein, human
  • T-Cell Acute Lymphocytic Leukemia Protein 1
  • Transcription Factors
  • TAL1 protein, human