UC Santa Cruz

Cancer is a genetic disease. All cancers are caused by and dependent on mutations. The widespread adoption of NGS in cancer research has revolutionized the field by allowing us to catalog the variants within and across cancer types. This knowledge was used to create a new taxonomy of cancers, where many tumors are classified by genetic alterations in addition to tissue of origin. Despite the role of NGS in identifying the mutations behind these new classifications, pre-genomic methods such as ISH and IHC are still commonly used in the clinic to identify relevant genetic alterations in tumors.About 20% of tumors worldwide are caused by viruses such as HPV, Epstein-Barr virus and Hepatitis B and C viruses. The virus may act as a mutagen by causing prolonged inflammation or by integration into the host genome. Viral infection can therefore be considered another type of genetic alteration used for the classification of tumors, and indeed some tumors are now classified by their causal viral infections. Epimutations are a type of genetic alteration affects epigenetic marks such as DNA methylation rather than the DNA sequence. Epimutations are the genetic lesions behind several disorders including cancer predisposition syndromes. Here I present my work developing an app that integrates with the UCSF 500 pipeline to detect known oncogenic viral sequences in DNA samples from tumors (Chapter 2). I also present my work analyzing long-read sequencing and methylation data of a patient with bilateral Wilms tumor to identify the epimutation causing their cancer predisposition syndrome previously missed by other technologies (Chapter 3). My work reflects the utility of adapting state-of-the-art sequencing technologies for diagnostic use in the clinic. H3K27M gliomas have a mutation in the genes encoding histone H3 that interferes with the deposition of the repressive epigenetic mark H3K27me3. This mark is important in regulating cell type development and EMT. In Chapter 4 I present my work using gene expression analysis to identify the role of EMT in the development and oncogenesis of H3K27M gliomas. Aberrant EMT may serve as a key dependency of these tumors.