Alterations in ATR in nasal NK/T-cell lymphoma and chronic active Epstein-Barr virus infection.
Nasal natural killer (NK)/T-cell lymphoma (NKTCL) and chronic active Epstein-Barr virus infection (CAEBV) are relatively frequent, especially in Asia, and are poor in prognosis. Both diseases are proliferative diseases of NK/T cells that show highly complicated karyotypes, suggesting the involvement of chromosomal instability. ATR is an important gene for DNA damage response and chromosomal stability. To evaluate the role of ATR gene alterations in the pathogenesis of NKTCL and CAEBV, the whole coding region of the ATR gene was examined in cell lines derived from NKTCL and CAEBV, as well as tumor samples from patients. ATR alterations were detected in two of eight NKTCL and in one of three CAEBV lines. Most aberrant transcripts observed were deletions resulting from aberrant splicing. ATR alterations were also detected in four of 10 NKTCL clinical samples. Both NKTCL and CAEBV cell lines with ATR alterations showed a delay or abrogation in repair of ionizing radiation-induced DNA double-strand breaks and ultraviolet-induced DNA single-strand breaks, and both exhibited a defect in p53 accumulation. These findings show that alterations in the ATR gene result in an abnormal response to DNA double-strand break and single-strand break repair, suggesting a role for ATR gene alterations in NKTCL lymphomagenesis.
Liu
Angen
A
Department of Pathology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
Takakuwa
Tetsuya
T
Luo
Wen-Juan
WJ
Fujita
Shigeki
S
Aozasa
Katsuyuki
K
D017398:Alternative Splicing; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D002908:Chronic Disease; D004247:DNA / Q000528:radiation effects; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D018450:Disease Progression; D020031:Epstein-Barr Virus Infections / Q000235:genetics*; D006801:Humans; D007694:Killer Cells, Natural / Q000473:pathology*; D016399:Lymphoma, T-Cell / Q000235:genetics*; D009154:Mutation; D009669:Nose Neoplasms / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014466:Ultraviolet Rays
D018797:Cell Cycle Proteins; D016159:Tumor Suppressor Protein p53; D004247:DNA; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases