| Personalized medicine and preventive care are major trends in current healthcare. The basis of personalized medicine is each person's unique genetic profile. In the case of cancer, genetic differences between normal and tumor tissues provide novel therapeutic targets or early and companion diagnostics markers. This thesis involves identifying germline and somatic mutations in polypeptide N-acetylgalactosaminyltransferase 12 (GALNT12) in human colon cancers and IgH gene rearrangements as plasma biomarkers in Non-Hodgkin's Lymphoma patients.;Aberrant glycosylation is a pathological alteration that is widespread in colon cancer, and usually accompanies the onset and progression of the disease. However, the genetic alterations underlying aberrant glycosylation remain largely unknown. We sequenced and analyzed N-acetylgalactosaminyltransferase 12 (GALNT12) gene in individuals with colon cancers and identified germline mutations.;New biomarkers with improved accuracy could be helpful for monitoring disease in patients with Non-Hodgkin's lymphomas (NHL). Towards this end, we have explored the feasibility of identifying the sequence of rearranged IgH genes using next-generation sequencing, then using PCR to detect specific rearranged DNA fragments in patients' plasma. In Chapter 3 we describe a novel IgH capture (IgCap) approach. Using this method, we were able to detect and precisely determine the sequence of rearranged IgH loci in the tumors of three NHL patients. Moreover, circulating rearranged DNA fragments could be identified in the plasma of all three patients. Even in cases wherein tumor biopsies were unavailable, we were able to use the IgH capture approach to identify rearranged DNA loci in the plasma of 8 of 14 patients. IgCap may enable more informed management of selected patients with NHL and other B-cell malignancies. |
