Genetic alteration is a rare event in breast and ovarian carcinoma associated stroma

AACR Centennial Conference: Translational Cancer Medicine-- Nov 4-8, 2007; Singapore B65 INTRODUCTION: Fibroblasts are a key component of human cancers. Co-culture and xenograft studies have shown that cancer associated fibroblasts (CAFs) play an important role in cancer initiation and progression. The tumour promoting ability of CAFs appears to be stable, suggesting that the cells might be programmed at the genetic or epigenetic level. Some studies have reported a high frequency of genetic aberrations in CAFs including Loss of Heterozygosity (LOH), microsatellite instability and point mutations in tumour suppressor genes and oncogenes, whereas other studies have reported very low or zero mutation rates. Consequently there is no consensus as to whether CAFs do or do not harbour cancer promoting gene mutations. To resolve this important issue, we undertook genome-wide analysis of epithelial and stromal components of 20 primary epithelial ovarian cancers, 10 primary epithelial breast cancers and five short term cultures of primary breast CAFs using the Affymetrix® GeneChip Human mapping 500K array which provides both copy number and LOH data. METHODS: Epithelial cells and tumour-juxtaposed stromal cells less than 5mm distant from the epithelial component were manually microdissected from fresh frozen ovarian and breast carcinoma biopsies. Cultured CAFs were purified from primay breast cancers using cell-type specific markers. Purified genomic DNA was analyzed using the 500K SNP array and results were compared with the matching normal DNA from blood lymphocytes. RESULTS: As expected a high frequency of genetic aberration was detected in the epithelial components of each tumour but LOH and copy number alterations were extremely rate in CAFs. CONCLUSIONS: The 500K SNP array platform has been demonstrated to be a reliable and high resolution genome-analysis platform. Our data does not support the existence of a very high frequency of genetic aberrations in CAF reprted in some studies. It is possible that other mechanisms, such as epigenetic changes, have a role in the tumour promoting phenotypes of CAFs.