Molecular characterization of a new recombination of the SIL/TAL-1 locus in a child with T-cell acute lymphoblastic leukaemia.
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.
Carlotti
Emanuela
E
Divisione di Ematologia, Ospedali Riuniti Bergamo, Clinica paediatrica, Università di Milano-Bicocca, Ospedale S. Gerardo, Monza, Italy.
Pettenella
Francesca
F
Amaru
Ricardo
R
Slater
Sarah
S
Lister
T Andrew
TA
Barbui
Tiziano
T
Basso
Giuseppe
G
Cazzaniga
Giovanni
G
Rambaldi
Alessandro
A
Biondi
Andrea
A
D000293:Adolescent; D000328:Adult; D051792:Basic Helix-Loop-Helix Proteins; D015139:Blotting, Southern / Q000379:methods; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D004268:DNA-Binding Proteins / Q000235:genetics*; D017353:Gene Deletion; D015321:Gene Rearrangement; D006801:Humans; D007223:Infant; D047908:Intracellular Signaling Peptides and Proteins; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics*; D015514:Oncogene Proteins, Fusion; D016133:Polymerase Chain Reaction / Q000379:methods; D011506:Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors / Q000235:genetics*
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D015514:Oncogene Proteins, Fusion; D011506:Proteins; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; C071236:STIL protein, human; C067143:TAL1 protein, human