生命科学学院2018年度秋季学期学术系列讲座之四
题目：Pan-cancer Genomic and Neoepitope Landscape of Pediatric Cancers
讲座人：Jinghui Zhang, Ph.D.
Chair, Department of Computational Biology, 
St. Jude Endowed Chair in Bioinformatics,
St. Jude Children’s Research Hospital, Memphis, Tennessee
时间：2018年10月16日（星期二），13:00-14:30
地点：生命科学学院邓祐才报告厅
主持人：吴虹教授
摘要：
Analysis of molecular aberrations across multiple cancer types, known as pan-cancer analysis, identifies commonalities and differences in key biological processes dysregulated in cancer cells from diverse lineages. Pan-cancer analyses have been performed for adult but not pediatric cancers, which commonly occur in developing mesodermic rather than adult epithelial tissues. Here we present a pan-cancer study of somatic alterations, including single nucleotide variants (SNVs), small insertion/deletions (indels), structural variations (SVs), copy number alterations (CNAs), gene fusions and internal tandem duplications (ITDs), in 1,699 pediatric leukemia and solid tumours across six histotypes, with whole-genome (WGS), whole-exome (WES) and transcriptome (RNA-seq) sequencing data processed under a uniform analytical framework. We report 142 driver genes in pediatric cancers, of which only 45% matched those found in adult pan-cancer studies and CNAs and SVs constituted the majority (62%) of events. Eleven genome-wide mutational signatures were identified, including one attributed to ultraviolet-light exposure in eight aneuploid leukemias. Transcription of the mutant allele was detectable for 34% of protein-coding mutations, and 20% exhibited allele-specific expression. These data provide a comprehensive genomic architecture for pediatric cancers and emphasize the need for pediatric cancer-specific development of precision therapies. We will also present a comprehensive analysis of potential neoepitopes derived from tumor-specific somatic mutations which can serve as promising targets for immunotherapy. The study, which involves analysis of missense mutations and oncogenic gene fusions identified in 540 childhood cancer genomes and transcriptomes representing 23 cancer subtypes, will facilitate the development of immunotherapeutic approaches designed for pediatric cancers.
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