ATR alterations in Hodgkin's lymphoma.
Hodgkin's lymphoma (HL) is characterized by the presence of neoplastic Hodgkin and Reed-Sternberg cells (HRSC) in a background of inflammatory cells. Free radicals and oxidative stress generated in the inflammatory lesions could cause DNA damage, thus providing a basis for lymphomagenesis. Ataxia-telangiectasia mutated (ATM) and Rad3-related (ATR) genes are responsive genes for DNA damage, therefore the potential involvement of the ATR gene in HL pathogenesis was examined in 8 HL cell lines and 7 clinical cases. ATR alterations were detected in 6 out of 8 HL lines. Most aberrant transcripts observed were heterozygous deletions, which may have resulted from aberrant splicing. ATR aberrant transcripts were also detected in 3 out of 7 clinical cases. Three alterations, del exon 4, deletion exon 29-34 and insertion of 137 bp in exon 46/47 were commonly observed in both cell lines and clinical samples. HL cells with ATR alterations except del exon 4 showed a delay/abrogation in repair for DNA double-strand breaks (DSBs) and single-strand break (SSB) as well as exhibiting a defect in p53 accumulation. These findings suggested the role of ATR gene alterations in HL lymphomagenesis.
Liu
Angen
A
Department of Pathology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
Takakuwa
Tetsuya
T
Fujita
Shigeki
S
Luo
Wen-Juan
WJ
Tresnasari
Kristianti
K
Van den Berg
Anke
A
Poppema
Sibrand
S
Aozasa
Katsuyuki
K
D000328:Adult; D000368:Aged; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000032:analysis / Q000235:genetics*; D045744:Cell Line, Tumor; D053960:DNA Breaks; D004260:DNA Repair; D005260:Female; D006689:Hodgkin Disease / Q000209:etiology / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D018797:Cell Cycle Proteins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases