Sigala, S. | Search bioRxiv

bioRxiv2023

The super-enhancer landscape reflects molecular subgroups of adrenocortical carcinoma

Adrenocortical carcinoma (ACC) is a rare cancer of the adrenal gland with generally very unfavourable outcome. Two molecular subgroups, C1A and C1B, have been previously identified with a significant association with patient survival. In this work, we study chromatin state organization characterized by histone modifications using ChIP-sequencing in adult ACC. We describe the super-enhancer landscape of ACC, characterized by H3K27ac, and identify super-enhancer regulated genes that play a significant role in tumorigenesis. We show that the super-enhancer landscape reflects differences between the molecular sub-groups C1A and C1B and identify networks of master transcription factors mirroring these differences. Additionally, we study the effects of molecules THZ1 and JQ1 previously reported to affect super-enhancer-driven gene expression in ACC cell lines. Our results reveal that the landscape of histone modifications in ACC is linked to its molecular subgroups and thus provide the groundwork for future analysis of epigenetic reprogramming in ACC.

cancer biology↗

bioRxiv2022

Innovative multidimensional models in a high-throughput-format for different cell types of endocrine origin

The adrenal gland provides an important function by integrating neuronal, immune, vascular, metabolic and endocrine signals under a common organ capsule. It is the central organ of the stress response system and has been implicated in numerous stress-related disorders. While for other diseases, regeneration of healthy organ tissue has been aimed at such approaches are lacking for endocrine diseases - with the exception of type-I-diabetes. Moreover, tumor formation is very common, however, appropriate high-throughput applications reflecting the high heterogeneity and furthermore relevant 3D-structures in vitro are still widely lacking. Recently, we have initiated the development of standardized multidimensional models of a variety of endocrine cell/tissue sources in a new multiwell-format. Firstly, we confirmed common applicability for pancreatic pseudo-islets. Next, we translated applicability for spheroid establishment to adrenocortical cell lines as well as patient material to establish spheroids from malignant, but also benign adrenal tumors. We aimed furthermore at the development of bovine derived adrenal organoids and were able to establish steroidogenic active organoids containing both, cells of cortical and medullary origin. Overall, we hope to open new avenues for basic research, endocrine cancer and adrenal tissue-replacement-therapies as we demonstrate potential for innovative mechanistic insights and personalized medicine in endocrine (tumor)-biology.

cancer biology↗