title: DNA polymerase theta is preferentially expressed in lymphoid tissues and upregulated in human cancers.
abstract: DNA polymerase theta (Pol theta) is a recently identified family A polymerase that contains an intrinsic helicase domain. Drosophila Pol theta mutants are hypersensitive to bifunctional DNA crosslinking agents and exhibit an elevated frequency of spontaneous chromosomal aberrations, suggesting a role for Pol theta in repair of DNA interstrand crosslinks and in the general maintenance of genome stability. To investigate a possible involvement of Pol theta in tumorigenesis, we have examined its expression in various normal and malignant tissues. Paired tumor and adjacent nontumorous tissues from patients with lung (n = 27), stomach (n = 28) and colon (n = 26) cancer, as well as 26 normal human tissues, were examined for Pol theta expression by RT-PCR, Northern or Western blot analysis. Pol theta was predominantly expressed in primary lymphoid organs including the fetal liver, thymus and bone marrow where lymphocyte progenitors undergo V(D)J rearrangements of their antigen receptor genes. In addition, Pol theta expression was upregulated in germinal center B cells, in which class switch recombination of the immunoglobulin genes occurs. Examination of Pol theta expression in matched cancer specimens revealed that Pol theta was barely detectable in the nontumorous tissues but was upregulated in 17 of 27 (63%) lung, 11 of 28 (39%) stomach and 20 of 26 (77%) colon cancers. Moreover, patients with high levels of Pol theta expression had a significantly poorer clinical outcome compared with those expressing low levels of Pol theta. These results implicate that Pol theta may have a specialized function in lymphocytes and that its overexpression may contribute to tumor progression.
authors.affiliation: Division of Pathology, Chiba Cancer Center Research Institute, Chiba, Japan.
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Kawamura
authors.forename: Rumana
authors.initials: R
authors.lastname: Bahar
authors.forename: Mika
authors.initials: M
authors.lastname: Seimiya
authors.forename: Masako
authors.initials: M
authors.lastname: Chiyo
authors.forename: Akihiko
authors.initials: A
authors.lastname: Wada
authors.forename: Seiji
authors.initials: S
authors.lastname: Okada
authors.forename: Masahiko
authors.initials: M
authors.lastname: Hatano
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tokuhisa
authors.forename: Hideki
authors.initials: H
authors.lastname: Kimura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Watanabe
authors.forename: Ichiro
authors.initials: I
authors.lastname: Honda
authors.forename: Shigeru
authors.initials: S
authors.lastname: Sakiyama
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Tagawa
authors.forename: Jiyang
authors.initials: J
authors.lastname: O-Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015152:Blotting, Northern; D015139:Blotting, Southern; D015153:Blotting, Western; D002469:Cell Separation; D002869:Chromosome Aberrations; D003110:Colonic Neoplasms / Q000201:enzymology; D004259:DNA-Directed DNA Polymerase / Q000096:biosynthesis*; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D008099:Liver / Q000196:embryology; D008175:Lung Neoplasms / Q000201:enzymology / Q000473:pathology; D008214:Lymphocytes / Q000378:metabolism; D008221:Lymphoid Tissue / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D017434:Protein Structure, Tertiary; D011995:Recombination, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000201:enzymology; D013950:Thymus Gland / Q000196:embryology; D014018:Tissue Distribution; D016896:Treatment Outcome; D015854:Up-Regulation; D000097462:DNA Polymerase theta
chemical_list: D004259:DNA-Directed DNA Polymerase; D000097462:DNA Polymerase theta