About me
The Impact of HDAC2 Deficiency in Uveal Melanoma
Location: West Ballroom
Mentor: Dr. Stefan Kurtenbach
Uveal Melanoma (UM) is the most common intraocular cancer in adults with a strong tendency to metastasize to the liver. Metastatic UM is resistant to therapeutic interventions, rendering it a fatal malignancy. A key predictor of metastasis is BAP1 loss, highlighting the role of epigenetic dysregulation in UM progression. Therapeutic methods targeting the epigenome of UM tumors, particularly with histone deacetylase (HDAC) inhibitors, are currently being explored in clinical trials.
The HDAC2 gene is located on chromosomal arm 6q, which is frequently lost in UM cells. Whole genome sequencing data from 80 UM tumors in The Cancer Genome Atlas (TCGA) reveal that some patients with 6q loss have additional deletions, leading to complete loss of HDAC2, an unexplored population in UM
My research entails investigating HDAC2 deficiency in UM via two approaches: generating an HDAC2 knockout (KO) UM cell line and identifying and propagating a naturally HDAC2-null UM cell line. Regarding the former, a transfection was performed on an HDAC2-proficient UM cell line (MP41) using an inducible Cas9 HDAC2 knockout lentivirus. Immunoblotting of this cell line revealed partial HDAC2 loss, prompting us to perform a serial dilution to isolate fully null clones. The second project entains screening a UM tissue array with Fluorescence in Situ Hybridization (FISH) to identify naturally HDAC2-null tumors. The FISH protocol was first optimized on MP41 cells and is now being adapted for tissue slides.
These models will enhance our knowledge on HDAC2’s role in UM pathology and treatment response while providing insight into the impact of HDAC2 deletion in UM patients. Identifying whether HDAC2 loss confers sensitivity or resistance to HDAC inhibitors will refine clinical trial strategies and aid in patient stratification for HDACi therapies.
