Rapid Detection of Somatic Mutations in Cancer Genes
Poster Feb 09, 2015
Michael J. Powell et. al.,
In the context of personalized cancer treatment, tumor mutation analysis by DNA sequencing has been
described frequently as the “gold standard”, yet DNA sequencing is one of the least sensitive methods
for characterizing mutation. At least 20% of a DNA population must be mutant for the mutation to be
detected by standard DNA sequencing. Implicit acceptance that this level of sensitivity is sufficient to characterize tumor mutations only makes sense if one assumes that tumors are monoclonal and that all the critical driver mutations will be present in the bulk of the tumor. Yet these are incorrect
assumptions. In fact, it has become clear that most if not all colon tumors are polyclonal and heterogeneous. Consequently, tumor driver mutations may not be detectable using standard DNA sequencing methods. In order to rapidly detect these low frequency mutations in tumor derived DNA we have developed a new technology that allows the detection of tumor driver and drug resistance somatic mutations at <0.1% sensitivity using quantitative PCR (qPCR) without the need for digital PCR or droplet digital PCR (ddPCR) methodology. We utilize xeno-nucleic acid (XNA) clamping probes that are specific for the target gene wild-type template and allow only the selective amplification of mismatched mutant templates. Direct detection of driver and drug resistance mutations within 2 hours of obtaining samples in KRAS, NRAS, BRAF, EGFR and JAK2 utilizing real-time qPCR with interchelating fluorescence dye detection.
Psychiatric Risk Gene Cacna1c and Early Life Stress: Potential Gene-Environment interactions?Poster
Early life stress (ELS) is highly associated with development of psychopathology
and mood disorders in adulthood. Genetic studies have identified variation in the gene calcium voltage-gated channel subunit alpha1C (CACNA1C) to increase risk for several psychiatric disorders. This poster assessed the expression of Cacna1c following prepubertal stress.
T-helper cell phenotype expression in cutaneous lesions of angioimmunoblastic T-cell lymphomaPoster
Angioimmunoblastic T-cell lymphoma (AITL) is a common type of peripheral T-cell lymphoma. AITL can be missed until lymphadenopathy develops in patients initially presenting with skin lesions, as skin biopsy may lack conclusive findings. Our case highlights the extranodal presentation of AITL with cutaneous lesions displaying the TFH phenotype.READ MORE
Novel Role of the Innate Immune DNA Sensor IFI16 (Interferon Gamma Inducible Protein 16) as a Major Epigenetic Modulator During KSHV Infection and Lytic ReactivationPoster
Studies have shown that IFI16 acts as an antiviral restriction factor against a number of DNA viruses, by inhibiting viral replication or transcription through epigenetic modifications. However, till date, no specific epigenetic function of IFI16 has been identified. Here, we have discovered that IFI16 recruits two histone methyltransferases on the KSHV episome leading to altered Histone H3K9 methylation, thus regulating its lifecycle.READ MORE