Chromosome walking on the TCL1 locus involved in T-cell neoplasia

Journal Article · Fri Oct 15 04:00:00 EDT 1993 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.90.20.9275· OSTI ID:5147423

Virgilio, L; Narducci, M G; Carotenuto, P; Camerini, B; Russo, G ^[1]; Isobe, Masaharu; Kurosawa, Nobuyuki ^[2]; Rushdi, A A; Croce, C M ^[3]

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1. Raggio-Talgene, Pomezia (Italy)
2. Toyama Medical and Pharmaceutical Univ. (Japan)
3. Jefferson Medical College, Philadelphia, PA (United States)

The TCL1 locus on chromosome 14 band q32.1 is frequently involved in the chromosomal translocations and inversions with the T-cell receptor genes observed in several T-cell tumors, including T-prolymphocytic leukemias, acute and chronic leukemias associated with the immunodeficiency syndrome ataxia-telangiectasia, and adult T-cell leukemia. All breakpoints cloned in this area have been mapped to 14q32.1, an area distant [approximately]10,000 kb from the immunoglobulin heavy-chain gene locus on chromosome 14q band 32.3. Except for two cases of inversion, no physical linkage of the cloned breakpoints has been reported, nor has a gene been identified in this region. Taking advantage of chromosome-walking techniques and of the P1 phage, the authors cloned and characterized 450 kb of the germ-line TCL1 locus, starting from the breakpoints of two independent T-cell leukemias. The authors show that all molecular rearrangements characterized so far map to these clones, indicating not only that this region is the target of chromosomal rearrangements occurring in this area but also that both inversion and translocations occur within a 300-kb region in the T-cell leukemias. In the attempt to identify a candidate oncogene responsible for the malignant transformation, a CpG island centromeric to the inversions and to the translocations has been identified. Two probes near the CpG island have detected sequences conserved among species, as well as two transcripts in the K562 human erythroleukemia cell line. On the basis of these data, a model of activation of the putative TCL1 oncogene is suggested. 30 refs., 4 figs.

• OSTI ID: 5147423
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States) Vol. 90:20; ISSN PNASA6; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

550400* -- Genetics
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CHROMOSOMAL ABERRATIONS
CHROMOSOMES
CLONING
CONNECTIVE TISSUE CELLS
DISEASES
DNA HYBRIDIZATION
DNA-CLONING
GENETIC MAPPING
HUMAN CHROMOSOME 14
HUMAN CHROMOSOMES
HYBRIDIZATION
IMMUNE SYSTEM DISEASES
LEUKEMIA
LEUKOCYTES
LYMPHOCYTES
MAPPING
MATERIALS
MUTATIONS
NEOPLASMS
SOMATIC CELLS