Abstract for presentation at 11th International Congress of Human Genetics

Expression Profiling of Familial Breast Tumours

  • Nic Waddell, Queensland Institute of Medical Research, Australia
  • kConFab Investigators, Peter MacCallum Cancer Centre, Australia
  • Dr Sunil Lakhani, University of Queensland Pathology, Australia
  • Dr Sean Grimmond, Institute for Molecular Biosciences, Australia
  • Dr Georgia Chenevix-Trench, Queensland Institute of Medical Research, Australia

    • Approximately 5% of women with breast cancer have a strong family history of disease but only 30-45% of severely affected families carry mutations in the predisposing genes BRCA1 and BRCA2, therefore other genes (‘BRCAx’) must be responsible for the burden of disease.. Expression profiling has recently shown that BRCA1, BRCA2 and BRCAx tumours have distinct expression profiles, and that there might be two classes of BRCAx tumours (Hedenfalk 2001 and 2003).
    We have used 46,000 oligo bead microarrays from Illumina to expression profile a cohort of 30 BRCA1, BRCA2 and BRCAx fresh frozen tumours from The Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab). Data analysis using ANOVA to determine which genes are differentially expressed in the BRCA1 and BRCA2 tumours identified genes involved in the regulation of cell cycle (including a protein phosphatase subunit, PP2R1A) and many genes with unknown function as well as genes that have not previously been associated with BRCA1 and BRCA2 tumours. Principle components analysis or clustering of these genes can clearly separate BRCA1 and BRCA2 tumours. A group of genes that were able to discriminate BRCAx from BRCA1 and BRCA2 tumours was also elucidated, including BRCA2, BCMP11 (Breast cancer membrane protein 11) and PIP (Prolactin induced protein). These discriminating genes will be tested in additional frozen breast tumours to see if they can be used to predict mutation status, and identify subclasses of BRCAx tumours. To further increase the sample size we will use DASL, a microarray platform from Illumina designed to analyse gene expression from formalin fixed paraffin embedded samples.

    Conference Organiser - ICMS Pty Ltd