Infrequent alteration in the p53R2 gene in human transitional cell carcinoma of the urinary tract.
OBJECTIVE
Functional defects in DNA repair have been shown to be associated with genomic instability followed by cancer. Recently, p53R2 [p53-inducible ribonucleotide reductase (RR) small subunit 2 homologous] was identified as a novel RR gene which is directly regulated by p53 protein in the G1 and G2 phases of the cell cycle supplying nucleotides to repair damaged DNA.


METHODS
We performed genetic analyses of p53R2 to determine whether p53R2 alterations play significant roles in urothelial tumorigenesis. Genomic DNA from 108 primary transitional cell carcinomas (TCCs; 81 of the urinary bladder and 27 of the renal pelvis or ureter) was analyzed for mutation in the p53R2 gene by direct sequencing. We focused on three domains of the p53R2 gene: one RR small subunit signature involving codons 120-146 (region 1) and two putative nuclear localization signal sequences, involving codons 149-155 (region 2) and codons 163-169 (region 3). In addition, a p53-binding site of 20 nucleotides in intron 1 of p53R2 was also analyzed.


RESULTS
One renal pelvic TCC (0.9%: 1/108) had a single-base substitution in p53R2 with a G to T transversion resulting in the amino acid substitution Glu136 --> Asp. This base substitution was localized within the domain of exon 4 encoding the RR small subunit signature, and causes an amino acid substitution in one of the most highly conserved regions of p53R2, in which human R2 and yeast RNR2 and RNR4 proteins are highly homologous.


CONCLUSIONS
This finding provides the in vivo evidence for the infrequent involvement of alterations in p53R2 inhuman urothelial TCCs.
Hayashi
Hideki
H
Division of Urology, Fujisaki Hospital, Saga, Japan.
Furihata
Mutsuo
M
Kuwahara
Morimasa
M
Kagawa
Susumu
S
Shuin
Taro
T
Ohtsuki
Yuji
Y
D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D001483:Base Sequence; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D012264:Ribonucleotide Reductases / Q000235:genetics*; D014571:Urologic Neoplasms / Q000235:genetics* / Q000473:pathology
D018797:Cell Cycle Proteins; D004273:DNA, Neoplasm; C405947:RRM2B protein, human; D012264:Ribonucleotide Reductases