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DNA polymerase beta gene mutations in human bladder cancer
J Matsuzaki1, Y Dobashi, H Miyamoto
1Department of Urology, Yokohama City University School of Medicine, Japan.
Abstract:
We examined 24 human bladder cancer tissues for possible mutations in the entire coding region of the human DNA polymerase beta gene using polymerase chain reaction analysis, single-strand conformational polymorphism analysis of RNA, and sequence analysis. DNA polymerase beta gene mutations were observed in four of the 24 cases (16.7%) and included three missense point mutations and a single base insertion. The single base insertion was also observed in our previous study of human prostate cancer, suggesting that this region may be a hot spot for mutation of the DNA polymerase beta gene. No clinical or pathological association was found among the four cases that contained the mutation. Three of the four cases with DNA polymerase beta gene mutation had mutations of the p16 or RB genes or loss of heterozygosity of the p53 and APC gene loci. The results of the study presented here suggest that DNA polymerase beta gene mutations, in combination with mutations of tumor suppressor genes, may be involved in certain cases of human bladder cancer.
Insights
Mutations in the DNA polymerase beta gene were found in 16.7% of bladder cancer tissues. These DNA polymerase beta gene mutations, alongside tumor suppressor gene alterations, may contribute to bladder cancer development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- DNA polymerase beta (Pol β) plays a crucial role in DNA repair.
- Mutations in DNA repair genes are implicated in various cancers.
- The role of Pol β mutations in human bladder cancer remains largely unexplored.
Purpose of the Study:
- To investigate the frequency and types of mutations in the entire coding region of the human DNA polymerase beta gene in bladder cancer tissues.
- To explore potential associations between Pol β mutations and clinical/pathological features.
- To examine the relationship between Pol β mutations and alterations in known tumor suppressor genes.
Main Methods:
- Analysis of 24 human bladder cancer tissues.
- Polymerase chain reaction (PCR) amplification of the entire coding region of the DNA polymerase beta gene.
- Single-strand conformational polymorphism (SSCP) analysis.
- Direct sequence analysis.
Main Results:
- Mutations in the DNA polymerase beta gene were identified in 4 out of 24 cases (16.7%).
- The observed mutations included three missense point mutations and a single base insertion.
- The single base insertion mutation was previously identified in prostate cancer, suggesting a potential mutation hot spot.
- No significant clinical or pathological associations were found for Pol β mutations.
- Three of the four cases with Pol β mutations also exhibited alterations in p16, RB, p53, or APC genes.
Conclusions:
- DNA polymerase beta gene mutations occur in a subset of human bladder cancers.
- The identified single base insertion may represent a mutation hot spot in the DNA polymerase beta gene.
- Combined mutations in DNA polymerase beta and tumor suppressor genes might play a role in the pathogenesis of some bladder cancers.