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Breakpoint of an inversion of chromosome 14 in a T-cell leukemia: sequences downstream of the immunoglobulin heavy chain locus are implicated in tumorigenesis

Journal Article · · Proc. Natl. Acad. Sci. U.S.A.; (United States)
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T-cell tumors are characterized by inversions or translocations of chromosome 14. The breakpoints of these karyotypic abnormalities occur in chromosome bands 14q11 and 14q32 - the same bands in which the T-cell receptor (TCR) ..cap alpha..-chain and immunoglobulin heavy chain genes have been mapped, respectively. Patients with ataxia-telangiectasia are particularly prone to development of T-cell chronic lymphocytic leukemia with such chromosomal abnormalities. The authors describe DNA rearrangements of the TCR ..cap alpha..-chain gene in an ataxia-telangiectasia-associated leukemia containing both a normal and an inverted chromosome 14. The normal chromosome 14 has undergone a productive join of TCR ..cap alpha..-chain variable (V/sub ..cap alpha../) and joining (J/sub ..cap alpha../) gene segments. The other allele of the TCR ..cap alpha..-chain gene features a DNA rearrangement, about 50 kilobases from the TCR ..cap alpha..-chain constant (C/sub ..cap alpha../) gene, that represents the breakpoint of the chromosome 14 inversion; this breakpoint is comprised of a TCR J/sub ..cap alpha../) segment (from 14q11) fused to sequences derived from 14q32 but on the centromeric side of C/sub ..mu../. These results imply that 14q32 sequences located at an undetermined distance downstream of immunoglobulin C/sub ..mu../ locus can contribute to the development of T-cell tumors.
Research Organization:
Medical Research Council Laboratory of Molecular Biology, Cambridge (England)
OSTI ID:
6408595
Journal Information:
Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 84:24; ISSN PNASA
Country of Publication:
United States
Language:
English

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Related Subjects

550401* -- Genetics-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
AUTORADIOGRAPHY
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGY
CARCINOGENESIS
CHROMOSOMAL ABERRATIONS
CHROMOSOMES
DAYS LIVING RADIOISOTOPES
DISEASES
DNA SEQUENCING
ELECTROPHORESIS
GENETIC MAPPING
GENETICS
GLOBULINS
HEMIC DISEASES
HETEROCHROMOSOMES
IMMUNE SYSTEM DISEASES
IMMUNOGLOBULINS
ISOTOPES
LEUKEMIA
LIGHT NUCLEI
MAPPING
MUTATIONS
NEOPLASMS
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
PATHOGENESIS
PATIENTS
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PROTEINS
RADIOISOTOPES
STRUCTURAL CHEMICAL ANALYSIS
TUMOR CELLS