Characterization of Isoform Usage, Novel Isoforms, and Tumor Evolution in Waldenström's Macroglobulinemia
Zachary Hunter
PhDDana-Farber Cancer Institute
Project Term: July 1, 2023 - June 30, 2024
The goals of this project can best be summarized with the following specific aims:
- To identify and functionally characterize novel isoforms and isoform dysregulation in Waldenstrom’s Macroglobulinemia;
- To investigate the mechanisms that underlie a novel form of post-transcriptional gene regulation in healthy donor B-cells that is absent in patients with Waldenstrom’s Macroglobulinemia;
- To conduct a multi-omic analysis of tumor evolution in Waldenstrom’s Macroglobulinemia by disease subtype
Most genes consist of discrete regions of DNA called exons that are stitched together to form a single transcript. This process allows for exons from the same gene to be skipped and/or combined in different ways to form unique versions of the gene called isoforms. These isoforms can have different and often opposing functions adding to an additional mechanism for cells to fine tune their signaling while responding to the environment and understanding which version of a gene is being expressed can be important for interpreting its biological impact on the cell. While most common isoforms have been described, there are still many undocumented isoforms in specific tissues or observed only in particular circumstances. Moreover, changes in DNA as well as the dysregulation of cellular processes that occur in cancer can alter isoforms and create new ones that can help the cancer cell grow and survive. In this study we propose to study these isoforms and the role they play in the evolution and subtypes of Waldenstrom’s Macroglobulinemia as well as their role in response to treatment and relapse.