Copy Number Variation Profiling For Patient Derived Xenograft

Xenograft is an important preclinical model.It is widely applied in medicine development against cancer and in researches of molecular mechanism of cancer.The continuous development of genomics and the high-throughput sequencing technology improves the genetics researches on xenograft.Colorectal carcinoma is a mortal cancer with high onset rate and death rate,thus it is important to gain more knowledge of genomics to advance the development and the screening of medicine for colorectal carcinoma.Genomic copy number variants play an important role in the development of cancer and the impact of drug response.Here we applied whole genome sequencing for four colorectal carcinomas and six corresponding xenografts at 62.89~100.01 X coverage to profile the whole genome copy number variation.In total,195.97~400.40 Mb and 384.37~1450.81 Mb copy number variants in length were detected for primary colorectal carcinomas and their corresponding xenografts.Further comparison of the copy number from primary tumors to their corresponding xenografts shows that the copy number on genome is very similar between them,with correlation coefficient of 0.636918~0.868897,significantly higher than that between random pairings(0.191743~0.420041).Also there is high similarity of copy number for 39 colorectal carcinoma related genes with correlation coefficient no less than 0.5 for 89.74% genes.These preservations on copy number profile indicate that copy number features are retained in xenografts during the plantation and growth in the hosts.In addition,there is expansion of copy number variant regions in xenografts' genome and a small fraction of copy number change compared to the primary tumors.These differences may explain the reasons of failure in clinical experiments,and at the meantime give support to preclinical experiments upon genetics.