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.