The Role of ATRX/DAXX loss in NF1-associated Solid Malignancies
Abstract
In this award period, we developed data that supported an important role for ATRX/DAXX loss and acquisition of ALT with an aggressive biology in NF1-associated gliomas, as well as a molecular subset of NF1-associated MPNSTs. This research effort is complementary to the research aim of the award but was completed using other funds available to the PI. In the laboratory, we demonstrate that ATRX knockdown results in ALT-like properties, including increased telomere lengths by PCR based methods and large telomeric foci using telomere specific FISH. ATRX knockdowns in MPNST-derived cell lines does not on its own result in an evident effect in cell growth. However, when the ATR inhibitor was administered, decreased growth in vitro was observed in a MPNST cell line that lacks TERT promoter alterations. These findings support a role of ATRX loss in a biologic subset of NF1-associated malignancies, and opens the opportunity for therapeutic targeting of these tumors using specific classes of drugs.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2019
- Accession Number
- AD1097112
Entities
People
- Fausto J Rodriguez
Organizations
- Johns Hopkins University