Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.2.8 (hypoxanthine-guanine phosphoribosyltransferase)
 2,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Somatic mutations are hallmarks of cancer progression. We sequenced 26 matched human prostate tumor and constitutional DNA samples for somatic alterations in the SRD5A2, HPRT, and HSD3B2 genes, and identified 71 nucleotide substitutions. Of these substitutions, 79% (56/71) occur within a WKVnRRRnVWK sequence (a novel motif we call THEMIS [from the ancient Greek goddess of prophecy]: W=A/T, K=G/T, V=G/A/C, R=purine (A/G), and n=any nucleotide), with one mismatch allowed. Literature searches identified this motif with one mismatch allowed in 66% (37/56) of the somatic prostate cancer mutations and in 74% (90/122) of the somatic breast cancer mutations found in all human genes analyzed. We also found the THEMIS motif with one allowed mismatch in 88% (23/26) of the ras1 gene somatic mutations formed in the sensitive to skin carcinogenesis (SENCAR) mouse model, after induction of error-prone DNA repair following mutagenic treatment. The high prevalence of the motif in each of the above mentioned cases cannot be explained by chance (P<0.046). We further identified 27 somatic mutations in the error-prone DNA polymerase genes pol eta, pol kappa, and pol beta in these prostate cancer patients. The data suggest that most somatic nucleotide substitutions in human cancer may occur in sites that conform to the THEMIS motif. These mutations may be caused by "mutator" mutations in error-prone DNA polymerase genes.
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PMID:Genomic analysis of cancer tissue reveals that somatic mutations commonly occur in a specific motif. 1862 41

Prostate cancer is the most commonly diagnosed malignancy in male populations in the Western world. The KLK15 gene, the newest member of the kallikrein family, is expressed in the prostate gland. The purpose of this study is the expression analysis and the clinical evaluation of the KLK15 mRNA spliced variants in prostate cancer (CaP) and benign prostatic hyperplasia (BPH) patients. Total RNA was isolated from 104 CaP and BPH tissue specimens. After testing the quality of the RNA, cDNA was produced by reverse transcription, and PCR was performed for the amplification of the KLK15 mRNA transcripts. GAPDH and HPRT genes were used as endogenous controls Our data revealed that mRNA spliced variants of KLK15 were differentially expressed in prostate tissue specimens. Analysis of data showed a statistically significant (P < 0.001) increase in the frequency of overexpression of KLK15 transcripts encoding for both the active isoform and for the isoform 3 in CaP compared to BPH samples. Furthermore, KLK15 transcripts were found to be highly expressed in more aggressive tumors (P = 0.017). These results suggest that KLK15 expression analysis could be employed as a valuable tool for the discrimination between BPH and CaP tissue specimens and as an unfavorable prognostic marker for prostate cancer.
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PMID:Expression analysis and study of the KLK15 mRNA splice variants in prostate cancer and benign prostatic hyperplasia. 2006 63