Proteins domain landscapes of somatic mutations in The Cancer Genome Atlas

Photo by Duncan Hull
Speaker Name: 
Thomas Peterson
Speaker Organization: 
UMBC, Baltimore, MD
Start Time: 
Wednesday, February 10, 2016 - 15:30
End Time: 
Wednesday, February 10, 2016 - 16:30
Intron Lounge
Joshua Stuart

    The fight against cancer has been hindered by its highly heterogeneous nature. Recent genome-wide sequencing studies have shown that individual malignancies contain many mutations that range from those commonly found in tumor genomes to rare cancer somatic mutations present only in a small fraction of lesions. Somatic mutations frequently found in tumor genomes often play a significant role in tumorigenesis or proliferation and are thus classified as driver mutations.
    Much work has been devoted towards identifying driver mutations in specific tissues, revealing the highly heterogeneous nature of driver mutations between different types of cancer. However, traditional methods for identifying genomic regions likely to harbor driver mutations are focused on whole genes or whole proteins, thus ignoring heterogeneous somatic mutation patterns between individual protein domains within the gene that can be unique to specific cancer types.
     In this work, we develop a protein domain-based approach to the analysis of somatic mutations from over five thousand sequenced tumors from The Cancer Genome Atlas (TCGA), revealing different regions within genes that play a role in different cancer types. Furthermore, we develop an approach based on aggregation of mutational data at the protein domain level, allowing the study of specific positions within domains across multiple genes that are biased towards being somatically mutated in cancer. By leveraging the structural and functional units of proteins in a protein domain-based framework, our analysis is able to identify novel driver mutation patterns unique to specific cancer types that would normally be missed by traditional gene-centric methods.

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Photo: flickr


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