Abstract for presentation at 11th International Congress of Human Genetics

Kallikrein 15 (KLK15): analysis of splice variants and single nucleotide polymorphisms, and their association with ovarian and prostate cancer

  • Ms Tracy O'Mara, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia
  • Ms Melanie Higgins, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia
  • Ms Lene Skeie, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia
  • Dr Ying Dong, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia
  • Dr Olivia Tan, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia
  • Ms Kimberly Hinze, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia
  • Dr John Yaxley, Brisbane Private Hospital, Brisbane, Australia
  • Prof Judith Clements, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia
  • Dr Amanda Spurdle, Queensland Institute of Medical Research, Australia
  • Dr Mary-Anne Kedda, Queensland Institute of Technology, Australia

    • Introduction: Ovarian and prostate cancers are hormone-related cancers that are often associated with poor clinical outcomes and high mortality. The kallikreins are a family of serine proteases that have been implicated in the aetiology of these diseases: kallikrein 15 (KLK15) has been shown to be upregulated and associated with poor prognosis in both ovarian and prostate cancer. We hypothesise that single nucleotide polymorphisms (SNPs) in the promoter region of the KLK15 gene will give rise to altered expression of this gene, and will be associated with ovarian and prostate cancer susceptibility and survival.
    Methods: We have used a bioinformatics approach to assess previously reported polymorphisms in the 5’ putative promoter region of KLK15. To further characterise the putative promoter region of KLK15, a region up to 11kb upstream of exon 1 has been PCR-amplified and sequenced in germline DNA from 30 women with aggressive ovarian cancer and 30 men with aggressive prostate cancer. EST databases have been used to predict KLK15 splice variants and we have used quantitative RT-PCR analysis to characterise the levels of expression of various splice variants in both normal and cancer cell lines.
    Results: In silico analyses have identified 34 previously validated and potentially functional SNPs within the putative promoter region of KLK15. Initial sequencing results from germline DNA have confirmed the presence of most of these SNPs in our population, and have identified a number of novel SNPs in patients with ovarian/prostate cancer. Investigation of EST databases suggested the presence of a new KLK15 splice variant and preliminary results suggest that this variant is highly upregulated in a prostate cancer cell line, LNCaP.
    Discussion: We have identified a new splice variant of the KLK15 gene that is upregulated in cancer cell lines and we will assess its importance in vivo through further expression analysis in tissue samples. We have also identified a number of novel SNPs in the promoter region of the KLK15 gene and we will examine the association of these SNPs with ovarian and/or prostate cancer predisposition and/or survival.

    Conference Organiser - ICMS Pty Ltd