FISH Detection of HER2 Amplification in Breast Cancer

Gene amplification is frequently detected in human tumor cells and is thought to make an important contribution to tumorigenesis (1 ,2 ). Systematic scanning of the whole genome of tumor cells using comparative genomic hybridization has revealed that gene copy number changes occur concurrently in many areas of the genome in solid tumors (3 ). Detailed analysis of altered regions of DNA has revealed complex DNA rearrangements often involving multiple genes and spanning several megabases in solid tumors. Overlaid on gene rearrangements are frequent changes in chromosome ploidy (4 –6 ). The analysis of amplified regions of DNA can lead to the identification of novel genes that contribute to tumorigenesis, but is complicated by the co-amplification of neighboring genes in these large, complex rearrangements. Many tumors show such a high degree of general DNA and chromosome rearrangement that some researchers argue the critical event in tumorigenesis is genomic instability (7 –10 ) with gene amplification being a consequence.