Performing Chromatin Immunoprecipitation (ChIP) in a Mouse Model Expressing Alveolar Soft Part Sarcoma (ASPSCR1-TFE3) to Understand Mechanisms of Cancer Progression

Background

Alveolar soft part sarcoma (ASPS) is a rare but deadly tumor found in the soft tissue. The peak of incidence occurs during adolescence or young adulthood. This neoplasm is driven by the translocation event between chromosome X and chromosome 17, which generates the fusion gene ASPSCR1-TFE3. Transcription factor E3 (TFE3) provides the nuclear localization and DNA binding in this chimeric fusion protein, while the functions of ASPSCR1 as a partner are relatively unknown. Because TFE3 is a master transcriptional regulator, it is hypothesized that ASPSCR1-TFE3 is a master regulator of alveolar soft part sarcomas.

While the sufficiency of ASPSCR1-TFE3 has been demonstrated in mouse models generated in the Jones lab, the function and breadth of transcriptional regulation is unknown. Research has been performed using ChIP-on-ChIP in cell lines systems to address this question. However, these models are limited and in order to truly understand such complicated networks it is best to study these protein-DNA interactions in the context of these tumors and their microenvironment (mouse models). As demonstrated previously, the microenvironment plays a crucial role in the development of these tumors.

Project Goal

Our goal is to perform ChIP-seq on ASPS tissue in order to delineate the network of signals that facilitate tumorigenesis and progression. We hope to gain a better understanding using a more patient applicable system and further investigate the processes of ASPCR1-TFE3 fusion genes in the context of ASPS.