About ACC

Adrenocortical carcinoma (ACC) is a rare tumor type with poor prognosis. Biomarkers to aid in the clinical and prognostic assessment are needed. Increased PTTG1 expression correlates with poor survival in patients with ACC. As immunohistochemistry (IHC) is a more practical clinical tool than genetic expression analysis, we assessed PTTG1 protein expression using IHC on tissue microarrays. We have worked with groups at MD Anderson and Cornell to gather two arrays that contain 67 ACC tumors, 34 adenomas and 30 normal adrenal glands. Nuclear PTTG1 protein expression was elevated in ACC but not adenomas or normal adrenals, and correlated with Ki67 expression, a known marker of poor prognosis. PTTG1 is a promising diagnostic and prognostic marker in the evaluation of adrenal tumors. This data is being submitted for publication in 2015. The group at TGen is continuing this collaboration to follow up on other proteins that may have diagnostic, prognostic or therapeutic value in ACC.
TGen scientists (Drs. Whitsett, Kim and Demeure) have also been instrumental in the genomic characterization of ACC by The Cancer Genome Atlas (TGCA), an organization tasked to create a genomic landscape across all tumor types. About one hundred ACC tumors (including those submitted by TGen) will have robust genomic and proteomic profiles, which represents the largest collection of ACCs ever examined. This database will serve as the benchmark for ACC towards investigations into diagnosis, prognosis and novel therapeutic strategies. The results have been submitted to a top-tier journal.
A new area of investigation that has emerged in the characterization of ACC is analysis the ‘methylome’. DNA methylation is a dynamic process used by the cell that employs a chemical modification to silence or activate gene expression. The observation of methylated or un-methylated DNA has significant impact on gene expression and can be used in diagnostic and therapeutic avenues. The methylation analysis of DNA from ACC tumors with gene expression has been performed at TGen. The results demonstrated differences in methylation between ACC and normal adrenal glands as well as between different ACC tumors, suggesting biomarkers for determining tumor from normal. Methylated genes were also identified that might impact ACC tumorigenesis and represent novel therapeutic targets. The results of this study have been submitted for publication.
Moreover, TGen’s high throughput screening (HTS) group started optimizing ACC cell lines derived from patients towards employment in high throughput (HT) assays. Thus far we have optimized 5 ACC cell lines that are ready for HT screening. Currently, we are in the process of performing high throughput compound screening with two ACC cell lines against a 2,400 compound library, most of which are FDA-approved drugs. This work is expected to be completed by mid-July, 2015. Such results will help to identify new treatment options for ACC patients by repurposing FDA-approved therapeutic avenues.

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