Sc-23 * the Role of Single Amino Acid Polymorphisms in Glioma Stem Cell Phenotypes
Year: 2014
Type: conference-abstract
Abstract: Recurrence of primary GBM is nearly inevitable and recurrent tumors are often more aggressive than the primary tumor. State-of-the-art sequencing and analysis methods have been applied to many tumor types, including GBM. While a large number of studies of genetic mutations and proteomic expression in GBM have been published, none have comprehensively examined the gene and protein expression of protein variants. This is due, in part, to the challenge in obtaining fresh material from patient specimens to study. Our panel of glioma stem cell lines (GSCs) have undergone comprehensive, quantitative analysis of their gene activity and proteomes. Proteins that normally have cell-protective properties, but harbor amino acid substitutions induced by single nucleotide polymorphisms (nsSNPs), may be transformed into proteins that promote genetic instability, dysregulate epigenetic control, and increase tumor invasivity. Those protein variants are not detected with conventional proteomic methods. To understand the role of protein-level expressed nsSNPs, which lead to single amino acid polymorphisms (SAAPs), in tumor invasivity and the resistance of GSCs to standard-of-care treatments, we established a novel, orthogonal bioinformatic approach to identify expressed protein SAAPs, a targeted proteomic analytical platform that enables the quantitation of SAAPs, and a phosphoproteomic approach to decipher GSC responses to pharmacological treatments. Using our novel analytical tools to study GSCs, we have already defined a set of eighteen protein SAAPs expressed in one or more cell lines that are implicated in the functional categories of DNA repair, transcriptional regulator, or protein kinase. We correlated the expression of protein variants with GSC phenotype, and defined patterns in intracellular signaling in GSCs in response to temozolomide (TMZ) and radiation treatments. The underlying molecular patterns are expected to help define the inadequate responses of GSCs to TMZ and radiation.
Source: Neuro-Oncology
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2058025987