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RNA-Sequencing Analysis of Adrenocortical Carcinoma, Pheochromocytoma and Paraganglioma from a Pan-Cancer Perspective
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology. Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Med Neuroendocrinol, NIH, 10 Ctr Dr,Bldg 10,Room 1E-3140, Bethesda, MD 20892 USA.ORCID iD: 0000-0003-0677-4894
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
Aix Marseille Univ, Dept Nucl Med, La Timone Univ Hosp, European Ctr Res Med Imaging, F-13385 Marseille, France.
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2018 (English)In: Cancers, ISSN 2072-6694, Vol. 10, no 12, article id 518Article in journal (Refereed) Published
Abstract [en]

Adrenocortical carcinoma (ACC) and pheochromocytoma and paraganglioma (PPGL) are defined by clinicopathological criteria and can be further sub-divided based on different molecular features. Whether differences between these molecular subgroups are significant enough to re-challenge their current clinicopathological classification is currently unknown. It is also not fully understood to which other cancers ACC and PPGL show similarity to. To address these questions, we included recent RNA-Seq data from the Cancer Genome Atlas (TCGA) and Therapeutically Applicable Research to Generate Effective Treatments (TARGET) datasets. Two bioinformatics pipelines were used for unsupervised clustering and principal components analysis. Results were validated using consensus clustering model and interpreted according to previous pan-cancer experiments. Two datasets consisting of 3319 tumors from 35 disease categories were studied. Consistent with the current classification, ACCs clustered as a homogenous group in a pan-cancer context. It also clustered close to neural crest derived tumors, including gliomas, neuroblastomas, pancreatic neuroendocrine tumors, and PPGLs. Contrary, some PPGLs mixed with pancreatic neuroendocrine tumors or neuroblastomas. Thus, our unbiased gene-expression analysis of PPGL did not overlap with their current clinicopathological classification. These results emphasize some importances of the shared embryological origin of these tumors, all either related or close to neural crest tumors, and opens for investigation of a complementary categorization based on gene-expression features.

Place, publisher, year, edition, pages
MDPI , 2018. Vol. 10, no 12, article id 518
Keywords [en]
pheochromocytoma, paraganglioma, adrenocortical carcinoma, adrenal tumor, pan-cancer analysis, neural crest, neuroendocrine
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-375237DOI: 10.3390/cancers10120518ISI: 000455199200056PubMedID: 30558313OAI: oai:DiVA.org:uu-375237DiVA, id: diva2:1283321
Available from: 2019-01-29 Created: 2019-01-29 Last updated: 2019-01-29Bibliographically approved

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Crona, JoakimBackman, SamuelWelin, StaffanHellman, PerStålberg, PeterSkogseid, Britt

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