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Mechanism of the t(14; 18) chromosomal translocation: structural analysis of both derivative 14 and 18 reciprocal partners

Journal Article · · Proc. Natl. Acad. Sci. U.S.A.; (United States)
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To elucidate the mechanism of the t(14;18)(q32;q21) chromosomal translocation found in follicular lymphoma, the authors examined the structure of both derivative (der) chromosomal breakpoints as well as their germ-line predecessors. They noted that chromosome segment 18q21 was juxtaposed with immunoglobulin heavy (H) chain gene diversity (D/sub H/) regions on all five der(18) chromosomes they examined, and they confirmed the juncture with immunoglobulin H-chain gene joining (J/sub H/) regions on the der(14) chromosome. However, the t(14;18) was not fully reciprocal in that chromosome 14 DNA between the D/sub H/ and J/sub H/ regions was deleted. Furthermore, extra nucleotides, reminiscent of N segments, were present at the der(14) and possibly der(18) junctions. This indicates that despite the mature B-cell phenotype of follicular lymphoma, the t(14;18) occurs during attempted D/sub H/-J/sub H/ joining, the earliest event in immunoglobulin rearrangement in a pre-B-cell. The detailed analysis of the germ-line 18q21 region indicated that most breakpoints clustered within a 150-base-pair major breakpoint region. A direct repeat duplication of chromosome 18 sequences was discovered at both chromosomal junctures, typical of the repair of a naturally occurring staggered double-stranded DNA break. These results prompt a translocation model with illegitimate pairing of a staggered double-stranded DNA break at 18q21 and an immunoglobulin endonuclease-mediated break at 14q32 and with N-segment addition, repair, and ligation to generate der(14) and der(18) chromosomes.
Research Organization:
National Institutes of Health, Bethesda, MD
OSTI ID:
6027016
Journal Information:
Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 84:8; 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
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BLOOD
BLOOD CELLS
BODY FLUIDS
CHROMOSOMAL ABERRATIONS
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DISEASES
DNA REPAIR
DNA SEQUENCING
GENES
GENETIC MAPPING
HYBRIDIZATION
ISOTOPES
LEUKOCYTES
LIGHT NUCLEI
LYMPHOCYTES
LYMPHOMAS
MAMMALS
MAN
MAPPING
MATERIALS
MUTATIONS
NEOPLASMS
NUCLEI
ODD-ODD NUCLEI
ONCOGENES
PATHOGENESIS
PHENOTYPE
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PRIMATES
RADIOISOTOPES
RECOVERY
REPAIR
SOMATIC CELLS
STRAND BREAKS
STRUCTURAL CHEMICAL ANALYSIS
VERTEBRATES