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Keylab Seminar by Dr. Siyuan Zheng
Authors:    Time:2017-02-20    Read:137

Speaker: Dr.Siyuan Zheng,

             Department of Genomic Medicine, MD Anderson Cancer Center

Time : 10:00, 23rd Feb. (Thursday )

Place :  Room 300
Host:Prof. Yixue LI

Title:From Data Driven to Question Driven: insights from high throughput profiling of the cancer genome.


Genome wide technologies have become increasingly important in cancer research. Large consortium projects such as The Cancer Genome Atlas (TCGA) have generated comprehensive genomic and epigenomic data that allow us to identify driver alterations, stratify relevant subtypes, and compare malignancies across tissue lineages. In this presentation, I will introduce our efforts in characterizing brain and adrenal cancers within TCGA, and how our integrated analysis leads to novel insights into carcinogenesis. We found in glioblastoma a breakpoint dense region on chr12q that resembles chromothripsis. Joint analysis of DNA rearrangements and transcript fusions suggests the pattern may result in a double minute structure that co-amplifies MDM2 and CDK4. Using whole genome and exome sequencing data, we modeled the evolution of glioblastoma recurrence. Clonal analysis revealed two clear evolutionary paths for primary tumors to recur. The clonal model manifests an expansion of the dominant clone of the primary disease, whereas the ancestral model suggests an early clonal seeds the recurrent disease that shares very few mutations with the primary tumor. Within TCGA, we as the working group characterized the genomic landscape of adrenocortical carcinoma. We found three consensus subtypes with distinct molecular feature and clinical outcome. Copy number analysis unveiled a surprising pattern of massive DNA loss followed by whole genome doubling. We found telomere shortening was associated with whole genome doubling, a finding that prompted us to examine telomere length across 31 human cancers. Results of this pan-cancer analysis suggest a previously underappreciated role of TERT promoter hypermethylation in reactivating TERT expression in cancer.

All are welcome!