title: Identification of single nucleotide polymorphisms in the human kallikrein 10 (KLK10) gene and their association with prostate, breast, testicular, and ovarian cancers.
abstract: 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Bhupinder B
authors.initials: BB
authors.lastname: Bharaj
authors.forename: Liu-Ying
authors.initials: LY
authors.lastname: Luo
authors.forename: Klaus
authors.initials: K
authors.lastname: Jung
authors.forename: Carsten
authors.initials: C
authors.lastname: Stephan
authors.forename: Eleftherios P
authors.initials: EP
authors.lastname: Diamandis
mesh_terms: D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics*; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D006801:Humans; D007610:Kallikreins / Q000032:analysis / Q000235:genetics*; D008297:Male; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013736:Testicular Neoplasms / Q000201:enzymology / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D004273:DNA, Neoplasm; C100936:KLK10 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen