Abstract for presentation at 11th International Congress of Human Genetics

Gene expression and mutational analysis of a minimal region of human chromosome 8p specifically disrupted in colorectal liver metastases

  • Dr Donia Macartney, Institute of Environmental Science and Research, New Zealand
  • Dr A Gibson, Wakefield GE Research Institute, New Zealand
  • Dr K Hood, Wakefield GE Research Institute, New Zealand
  • Dr A Croft, Wakefield GE Research Institute, New Zealand
  • Dr H Shi, Wakefield GE Research Institute, New Zealand
  • Dr R Lea, Institute of Environmental Science and Research, New Zealand
  • Dr S Rooker, Wellington Hospital, New Zealand
  • Mr R Stubbs, Wakefield GE Research Institute, New Zealand

    • Colorectal cancer (CRC) is the fourth most common cancer worldwide. Liver metastasis occurs in about 50% of patients and is the major cause of death. Loss of chromosome 8p is frequently seen in CRC and a number of studies suggest 8p involvement in metastasis.
    Loss of heterozygosity analyses of matched patient normal, colon tumour (CT) and liver metastases (LM) samples identified a minimal region of metastases-specific loss (<800kb) on human chromosome 8p. Further characterisation involved gene expression analyses at the RNA level using real-time PCR for 14 genes in LM samples from 34 individuals of which matching CT material was available for 14 and colon normal for 6/14. Mutational analyses were performed on 4 genes and confirmatory immuno-histochemistry and Western blot analyses on a number of samples. Real-time gene expression and polymorphism data were analysed for associations with clinical parameters.
    Statistical analyses revealed interesting observations including: the TRAIL-related gene cluster and DBC2 (deleted in breast cancer 2) demonstrating a degree of co-ordinate regulation at the transcriptional level in liver metastases; a known DR4 polymorphism appeared to be associated with colon tumour APCS staging (p<0.01); a known DR5 polymorphism appeared to be associated with primary tumour site (p<0.01); a significant decrease in ADAMDEC transcript in colon tumour and liver metastases samples compared to normal colon.
    This gene rich region may prove to be critical in the progression of cancer with disruption causing a cascade of perturbations significantly increasing the risk of successful metastasis. Thus this region of 8p may provide the basis for the development of both predictive molecular/diagnostic markers or new drug targets. The identification of patients, either with micrometastases, or at risk of metastases, could significantly aid the treatment of CRC and potentially lead to better patient outcome.

    Conference Organiser - ICMS Pty Ltd