![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
Tools
Tools
Preview |
PDF (Original Article)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
6MB |
![[thumbnail of Supplemental Material]](https://edoc.mdc-berlin.de/style/images/fileicons/other.png) |
Other (Supplemental Material)
155kB |
| Item Type: | Article |
|---|---|
| Title: | Cellular landscape of adrenocortical carcinoma at single-nuclei resolution |
| Creators Name: | Tourigny, D.S., Altieri, B., Secener, A.K., Sbiera, S., Schauer, M.P., Arampatzi, P., Herterich, S., Sauer, S., Fassnacht, M. and Ronchi, C.L. |
| Abstract: | Adrenocortical carcinoma (ACC) is a rare yet devastating tumour of the adrenal gland with a molecular pathology that remains incompletely understood. To gain novel insights into the cellular landscape of ACC, we generated single-nuclei RNA sequencing (snRNA-seq) data sets from twelve ACC tumour samples and analysed these alongside snRNA-seq data sets from normal adrenal glands (NAGs). We find the ACC tumour microenvironment to be relatively devoid of immune cells compared to NAG tissues, consistent with known high tumour purity values for ACC as an immunologically "cold" tumour. Our analysis identifies three separate groups of ACC samples that are characterised by different relative compositions of adrenocortical cell types. These include cell populations that are specifically enriched in the most clinically aggressive and hormonally active tumours, displaying hallmarks of reorganised cell mechanobiology and dysregulated steroidogenesis, respectively. We also identified and validated a population of mitotically active adrenocortical cells that strongly overexpress genes POLQ, DIAPH3 and EZH2 to support tumour expansion alongside an LGR4+ progenitor-like or cell-of-origin candidate for adrenocortical carcinogenesis. Trajectory inference suggests the fate adopted by malignant adrenocortical cells upon differentiation is associated with the copy number or allelic balance state of the imprinted DLK1/MEG3 genomic locus, which we verified by assessing bulk tumour DNA methylation status. In conclusion, our results therefore provide new insights into the clinical and cellular heterogeneity of ACC, revealing how genetic perturbations to healthy adrenocortical renewal and zonation provide a molecular basis for disease pathogenesis. |
| Keywords: | Adrenal Gland, Cancer, Molecular Oncology, Single Cell, Tissue Homeostasis |
| Source: | Molecular and Cellular Endocrinology |
| ISSN: | 0303-7207 |
| Publisher: | Elsevier |
| Volume: | 590 |
| Page Range: | 112272 |
| Date: | 1 September 2024 |
| Official Publication: | https://doi.org/10.1016/j.mce.2024.112272 |
| PubMed: | View item in PubMed |
Repository Staff Only: item control page
