[基础医学]生物信息学 高通量癌症研究.pdf

基于高通量测序技术的癌症研究 林钊 linzhao@genomics.cn Cancer Background CACER GENOMICS n Cancers are caused by changes that have occurred in the DNA sequence of the genomes of cancer cells n Characteristic: The high heterogenicity in the different cancer tissue,different developing period n Target: ü a comprehensive catalogue of somatic mutations cancer samples ü identification of further potentially druggable cancer genes ü utility of somatic mutations as biomarkers for prognosis hypothesis-driven data-driven, large scale analysis Problems and difficulties of classical methods  Unable to detect rare variants ，MAF5%.  Rare SNPs were true diseases risk variants.  Classical methods have just looked at cancer cells and sequenced genes known or suspected to be linked to cancer,it may overlooked key mutations, especially new ones.  Hypothesis genes chosen, long cycle time and low successful rate. 6 All these can be solved by sequencing It ’s time to sequencing ！ MR Stratton et al. Nature 458, 719-724 (2009) 7 Overview of Cancer Solutions Exome Whole Cell line Single-cell sequencing genome sequencing sequencing Research 100 tumor 10 groups whole 50X exome design and 100 (blood+ genome of 20 normal control 50X tumor tissue) sequencing an