Chromosome translocations and fusion genes in breast cancer.

Abstract #2021 Background: Little is known about chromosome translocations in the common epithelial cancers such as breast cancer, in spite of the central role played by translocations and consequent gene fusions in haematopoietic cancers.
 Methods: We present a comprehensive analysis by array painting of the chromosome translocations of four breast cancer cell lines, DU4475, HCC1806, HCC1187 and ZR-75-30. In array painting chromosomes are isolated by flow cytometry, amplified and hybridized to DNA microarrays. All breakpoints, totalling nearly 250, were mapped to at least 1Mb resolution and most balanced breakpoints were mapped to about 2kb resolution using custom oligonucleotide arrays. The remaining unbalanced breakpoints were mapped to around 20kb by identifying copy number steps in Affymetrix SNP6 array hybrizations obtained by the Sanger Institute9s Cancer Genome Project. Breast tumours in parraffin section in tissue microarrays were screened by FISH to see whether selected breakpoints found in the cell lines are present in breast tumours.
 Results: We found at least 12 reciprocal translocations in the four cell lines, substantially more than expected, and many more rearrangements were balanced for at least one participating chromosome. Many of the breakpoints were within or adjacent to cancer-relevant genes, and three of the translocations have already been shown to form fusion transcripts, RIF1-PKD1L1, PUM1-TRERF1 and TAX1BP1-AHCY. For selected genes targetted by the translocations, about 100 breast tumours were screened for breaks. Breaks were found in two to six cases for several of the genes, confirming that some of them were broken in breast tumours. For example two cases of unbalanced breakage were identified in PKD1L1, and these were confirmed by array-CGH.
 Discussion: Our results suggest that breast cancers have fusion genes, and support the emerging view that chromosome rearrangements are likely to play a significant role in common epithelial cancers. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2021.