Identification of single nucleotide polymorphisms in the human kallikrein 10 (KLK10) gene and their association with prostate, breast, testicular, and ovarian cancers
| Autor: | Klaus Jung, Liu-Ying Luo, Bhupinder B. Bharaj, Carsten Stephan, Eleftherios P. Diamandis |
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| Rok vydání: | 2002 |
| Předmět: |
Male
Tumor suppressor gene Urology Down-Regulation Single-nucleotide polymorphism Breast Neoplasms KLK10 Biology medicine.disease_cause Polymerase Chain Reaction Polymorphism Single Nucleotide Exon Testicular Neoplasms Genotype medicine Gene family Humans Ovarian Neoplasms Cancer Prostatic Neoplasms DNA Neoplasm Sequence Analysis DNA Prostate-Specific Antigen medicine.disease Up-Regulation Oncology Cancer research Female Kallikreins Carcinogenesis |
| Zdroj: | The Prostate. 51(1) |
| ISSN: | 0270-4137 |
| Popis: | Background The KLK10 gene (also known as the normal epithelial cell-specific 1 gene) is a member of the expanded human kallikrein gene family. Recently, it has been reported that KLK10 is a tumor suppressor gene and that its expression is downregulated in various forms of cancer and cancer cell lines. KLK10 is also upregulated in ovarian cancer. We thus hypothesized that the KLK10 gene may be a target for mutations in various cancers. Methods We sequenced the five coding exons of the KLK10 gene using genomic DNA from various tumors, normal tissues, and blood, by PCR amplification and automated sequencing. Results In none of the tumor-derived DNAs, we identified somatic mutations that could inactivate this gene. However, we identified a prevalent germline single nucleotide variation at codon 50 (exon 3) of this gene [GCC (alanine) to TCC (serine)]. The GCC genotype was less prevalent in prostatic cancer patients in comparison to control subjects (P = 0.027) but no differences were seen with testicular, ovarian, and breast cancer. We also identified four genetic variations in exon 4, at codons106 [GGC (glycine) to GGA (glycine)], codon 112 [ACG (threonine) to ACC (threonine)], codon 141 [CTA (leucine) to CTG (leucine)], and at codon 149 [CCG (proline) to CTG (leucine)]. None of these variations was significantly different between normal subjects and cancer groups. Conclusions We found no evidence for somatic mutations of the KLK10 gene in cancers of the prostate, breast, ovary, and testis. The single nucleotide variation at codon 50 appears to be associated with prostate cancer risk. Prostate 51:35–41, 2002. © 2002 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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