The Role of ATRX/DAXX loss in NF1-associated Solid Malignancies
Abstract
In this award period, we demonstrated that ATRX knockdown results in ALT-like properties, including increased telomere lengths by PCR based methods and large telomeric foci using telomere specific FISH in MPNST. To more accurately model ATRX loss and ALT in NF1-associated tumors we performed CRISPR mediated TERC knockouts in MPNST cell lines with ATRX loss and are currently characterizing the best clones for in vivo experiments. Our preliminary data demonstrates that the knockdown is successful, that the cells continue to grow, and they lack the expression of senescence markers. We are confident that these models will provide new insights into the role of ATRX loss in the context of NF1-associated tumors and a possible therapeutic role for ATR inhibitors in these difficult to treat tumors.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2020
- Accession Number
- AD1113587
Entities
People
- Fausto J Rodriguez
Organizations
- Johns Hopkins School of Medicine