Talk Title: Computational analysis of mutations in tumors reveals unexpected carcinogenic exposures
Somatic DNA mutations are a major cause of cancer, and there is an unmet need for improved assessment of the roles of specific mutagens in causing cancer. Cheap cancer-genome sequencing has created a novel opportunity to meet this need via analysis of mutational signatures. This analysis links mutagens to identifiable patterns of somatic mutations, which are composed of features such as single-base-pair and double-base pair substitutions and small insertions and deletions in the context of flanking bases. These patterns are typically analyzed in the context of the genomic landscape of transcription and DNA replication. We take as a prominent example aristolochic acid (AA), a mutagen and kidney toxin found in some herbal medicine. The mutational signature of AA now implicates it > 75% of liver cancers in Taiwan and 20% to 40% of liver cancers in Southeast Asia and China and Southeast Asia. Mutational signature analysis also implicates AA in Asian urinary tract and bile duct cancers. The prevalence of AA mutations in tumors has broad public health implications and highlights the need for additional prevention efforts by means of regulation and education. We will further discuss the computational techniques used in mutational signature analysis and present some unresolved challenges.
Steven G. Rozen PhD, Director, Duke-Nus Centre For Computational Biology, Professor, Cancer And Stem Cell Biology Program, Associate Dean Of Research Informatics Duke-Nus (Singapore), Interim Cio Prism (Precision Medicine Institute Of Singhealth And Duke-Nus)
Steve Rozen’s research has spanned bioinformatics, human genetics and cancer genomics. He created and maintains the widely-used Primer3 software for PCR primer design. He also worked extensively on identifying mutations in human Y chromosomes and their clinical consequences, as reported in multiple publications in Nature Genetics and Nature. Rozen founded and directs the Duke-NUS Centre for Computational Biology. The Centre’s faculty have published > 140 scientific papers since 2011 and the Centre offers a PhD program in bioinformatics. Rozen’s own laboratory now focuses on bioinformatics and cancer genomics, and is part of a team-science effort in cancer genomics that has led to multiple papers, including 5 in Nature Genetics. Areas of focus within cancer genomics include alternative splicing, lncRNAs, and use of mutational signatures as tools for studying carcinogenesis and the molecular epidemiology of cancer.