Cancer genomes are characterized by changes in the genome on many different levels. In breast cancer, the HER2 amplicon is very important, but is not been well understood. It is known that the genes in the region of HER2 are increased in copy number, but the exact organization of the amplicon in cancer cells is not known. There is the potential for rearrangements between the genes and for different segments of the amplicon to exist and varied copy numbers. We have used long read sequencing of primary breast cancers to determine their HER2 amplicon structure. Another source of tumor gene variation is the development of fusion proteins that result from genome rearrangements. These fusion proteins are a key driver of oncogenesis and are important in the treatment of cancers. To overcome the drawbacks of short reads for fusion RNA detection, we have used long read sequencing to sequence the full cDNAs of fusions proteins. We have investigated samples from prostate cancer, breast cancer and leukemia and have novel insights into the cancer development and potential for treatment.
