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

• Published in: British journal of haematology Vol. 118; no. 4; pp. 1011 - 1018
• Main Authors: Carlotti, Emanuela, Pettenella, Francesca, Amaru, Ricardo, Slater, Sarah, Lister, T. Andrew, Barbui, Tiziano, Basso, Giuseppe, Cazzaniga, Giovanni, Rambaldi, Alessandro, Biondi, Andrea
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.09.2002; Blackwell
• Subjects: Adolescent; Adult; Basic Helix-Loop-Helix Transcription Factors; Biological and medical sciences; Blotting, Southern - methods; breakpoint; Child; Child, Preschool; Chromosome Mapping; Chromosomes, Human, Pair 1; DNA-Binding Proteins - genetics; Gene Deletion; Gene Rearrangement; Hematologic and hematopoietic diseases; Humans; Infant; Intracellular Signaling Peptides and Proteins; Leukemia-Lymphoma, Adult T-Cell - genetics; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Oncogene Proteins, Fusion; PCR; Polymerase Chain Reaction - methods; Proteins - genetics; Proto-Oncogene Proteins - genetics; SIL; T-Cell Acute Lymphocytic Leukemia Protein 1; TAL‐1; Transcription Factors - genetics; T‐ALL; Human; Breakpoint; Acute; Clinical form; Malignant hemopathy; Case study; Polymerase chain reaction; Lymphoproliferative syndrome; Genetics; Acute lymphocytic leukemia; Molecular biology; Child; Hybrid gene
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1046/j.1365-2141.2002.03747.x

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.