Abstract for presentation at 11th International Congress of Human Genetics

Analysis of a large familial prostate cancer pedigree using comparative genomic hybridisation

  • Liesel FitzGerald, Menzies Research Institute, Australia
  • Dr Jim Stankovich, Walter and Eliza Hall Institute, Australia
  • Mr Gareth Price, Mater Medical Research Institute, Australia
  • Dr James McKay, International Agency for Research in Cancer, France
  • Prof Deon Venter, Mater Medical Research Institute, Australia
  • Dr Jo Dickinson, Menzies Research Institute, Australia

    • Although there have been a number of comparative genomic hybridisation (CGH) studies examining prostate cancer (PC) tumours, there have been none investigating multiple cases within families. In the two previous familial PC CGH studies, only single cases within families were examined using low resolution metaphase spreads.
    Our study investigated a large Tasmanian familial PC pedigree using the method of array CGH. A total of 16 formalin-fixed and paraffin embedded PC tissue samples were studied. These tumours were PALM dissected, degenerate oligonucleotide amplified, and labelled for fluorescence detection by high-resolution BAC aCGH, a technique providing an average resolution of ~1.4Mb. All tumours displayed genetic alterations. The most common losses were found at chromosomal regions 1p22, 1q24, 5q13, 6p25, 6q22, 6q26, 7p21, 17p13 and 19p13. The most common gains were found at 1p36, 1p34, 6p24, 6q26, 17p13 and 20p12. While several of these genetic changes are unique to this and previous familial studies, e.g. loss at 19p13 and gain at 17p13, there were also changes common to sporadic studies, e.g. loss at 1p22 and gain at 6p24. A number of losses observed here have also previously been associated with progression or metastasis of PC e.g. 5q and 6q. Two of the most common losses found in previous sporadic PC studies, 16q and 18q, occurred rarely or not at all in this family.
    The results from this study suggest that the genetic alterations common to both familial and sporadic tumours may be related to biological events downstream of cancer initiation, such as progression and metastasis of the tumour. The cellular changes unique to familial PC found here and in the previous two studies, suggest that germline mutations may initiate different genetic pathways from those found in sporadic PC. This study has provided insights into the similarities and differences between familial and sporadic PC, and presents a framework for further work in this area.

    Conference Organiser - ICMS Pty Ltd