Abstract
Purpose :
Lacrimal gland adenoid cystic carcinoma (LGACC) is a rare but highly lethal indolent cancer originating in the cells of secretory glands, primarily of the head and neck. With the 10-year survival rate of 20%, the only life extending technique is to remove the eye and surrounding socket contents followed by extensive chemoradiation. Despite radical treatment, LGACC has a poorer prognosis than head and neck adenoid cystic carcinoma (ACC) in part due to its propensity for perineural invasion, and hematogenous and intracranial spread. Extensive genome analysis of adenoid cystic carcinoma (ACC) of the head and neck has uncovered a high mutation rate of MYB that leads to overexpression. This event is thought to be the key driving mutation of ACC that has been well characterized in tissue samples. A pressing issue in the field of ACC research is the loss of MYB expression in cell lines developed from tumor tissue. As MYB overexpression is a key characteristic of ACC, it is important for cell line models to maintain the overexpression. Here, we develop the tools and cell lines essential for the molecular and in vitro characterization of MYB in LGACC.
Methods :
We completed RNA sequencing on our 12 LGACC cell lines and identified a loss of MYB expression, consistent with head and neck ACC cell lines. To address this issue, we transduced 3 LGACC and 3 normal lacrimal gland cell lines with a dual vector system that includes tet-inducible MYB expression to reintroduce its overexpression in the LGACC cells. We validated MYB overexpression via RT-qPCR and western blot. We completed RNA sequencing on our newly developed cell lines and have studied the effects of reintroducing MYB expression in migration and proliferation assays.
Results :
We developed new LGACC cell lines with inducible MYB expression, essential for downstream in vitro characterization of this key molecular driver underlying cancer progression in patients. We characterized how the overexpression of MYB in normal and LGACC cells changes the proliferation and migration.
Conclusions :
To advance the understanding and treatment of LGACC, there is a need for a validated model to be able to LGACC in-vitro. We have developed cell line models that have regained the main driver of ACC. This now allows us to further understand the role of MYB in LGACC progression and have a model to test treatments.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.