AUG 20, 2014 8:00 AM PDT

High-resolution genomic analysis reveals genetic impacts of human papillomavirus in human cancers

Speaker
  • Assistant Professor Department of Molecular Virology, Immunology and Medical Genetics, Assistant Professor, Division of Hematology, Department of Internal Medicine, Human Cancer Genetics Prog
    BIOGRAPHY

Abstract

One of the hallmarks of human cancers is genetic instability. My colleagues and I recently identified a remarkable association between human papillomavirus (HPV) and genomic structural variation in flanking host genomic DNA, both in human cancer cell lines and primary tumors. A combination of whole-genome sequencing and other molecular assays revealed HPV integrants frequently adjacent to and bridging extensively amplified and rearranged genomic sequences, including deletions, inversions, and chromosomal translocations. We developed a model of looping to explain these data. Our model suggests that HPV integrant-mediated DNA replication and recombination may result in viralhost DNA concatemers, frequently disrupting genes involved in oncogenesis and amplifying the HPV oncogenes E6 and E7. Using innovative new long-range deep sequencing methods, we currently are characterizing in detail these genomic structural variants, induced by HPV integration in primary human cancers. Use of such high-resolution genomics methods has shed new light on a catastrophic process, distinct from chromothripsis and other mutational processes, by which HPV can induce genomic instability and disrupt candidate cancer-causing genes.


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AUG 20, 2014 8:00 AM PDT

High-resolution genomic analysis reveals genetic impacts of human papillomavirus in human cancers



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