Abstract
Objective:
To investigate the possible relationship between defects in the FA/BRCA pathway of genomic stability and potential pathogenesis of T and B cell lymphoma.
Methods:
Nineteen cell lines derived from diverse subtypes of lymphoma for possible FA pathway defects were screened.
Results:
No defect in FANCD2 ubiquitination was observed. However, the FANCN protein was absent in cell lines HT and Sudhl4. This absence was correlated with enhanced MMC-induced G2 arrest, growth inhibition and high chromosomal breakage rate in both cell lines. In addition, in exon-5a of FANCN gene, a mutation of c.1769 C>T, p. A590V was found in cell line HT, but not in cell line Sudhl4.
Conclusion:
This mutation may be the reason causing the absence of the FANCN protein expression or making the protein unstable and losing its function.
MeSH terms
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Animals
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Antibiotics, Antineoplastic / pharmacology
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BRCA2 Protein / metabolism*
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Base Sequence
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Cell Cycle / drug effects
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Chromosome Breakage / drug effects
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Fanconi Anemia / metabolism*
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Fanconi Anemia Complementation Group D2 Protein / metabolism
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Fanconi Anemia Complementation Group N Protein
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Gene Expression Regulation, Neoplastic
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Genomic Instability
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Humans
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Lymphoma / genetics
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Lymphoma / pathology*
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Mitomycin / pharmacology
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Molecular Sequence Data
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Mutation
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Nuclear Proteins / chemistry
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Nuclear Proteins / deficiency
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Protein Stability
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Sequence Analysis, DNA
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Signal Transduction*
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Tumor Suppressor Proteins / chemistry
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Tumor Suppressor Proteins / deficiency
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / metabolism
Substances
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Antibiotics, Antineoplastic
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BRCA2 Protein
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Fanconi Anemia Complementation Group D2 Protein
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Fanconi Anemia Complementation Group N Protein
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Nuclear Proteins
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PALB2 protein, human
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Tumor Suppressor Proteins
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Mitomycin