Targeted RNAseq of Formalin-Fixed Paraffin-Embedded Tissue to Differentiate Among Benign and Malignant Adrenal Cortical Tumors
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- Samuel W. Plaska
- Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA
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- Chia-Jen Liu
- Michigan Center for Translational Pathology, Ann Arbor, Michigan, USA
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- Jung Soo Lim
- Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA
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- Juilee Rege
- Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA
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- Nolan R. Bick
- Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA
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- Antonio M. Lerario
- Department of Internal Medicine, Division of Metabolism, Endocrinology, and Diabetes, University of Michigan Medical School, Ann Arbor, Michigan, USA
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- Gary D. Hammer
- Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA
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- Thomas J. Giordano
- Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA
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- Tobias Else
- Department of Internal Medicine, Division of Metabolism, Endocrinology, and Diabetes, University of Michigan Medical School, Ann Arbor, Michigan, USA
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- Scott A. Tomlins
- Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA
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- William E. Rainey
- Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA
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- Aaron M. Udager
- Michigan Center for Translational Pathology, Ann Arbor, Michigan, USA
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説明
<jats:title>Abstract</jats:title><jats:p>Lack of routine fresh or frozen tissue is a barrier to widespread transcriptomic analysis of adrenal cortical tumors and an impediment to translational research in endocrinology and endocrine oncology. Our group has previously pioneered the use of targeted amplicon-based next-generation sequencing for archival formalin-fixed paraffin-embedded (FFPE) adrenal tissue specimens to characterize the spectrum of somatic mutations in various forms of primary aldosteronism. Herein, we developed and validated a novel 194-amplicon targeted next-generation RNA sequencing (RNAseq) assay for transcriptomic analysis of adrenal tumors using clinical-grade FFPE specimens. Targeted RNAseq-derived expression values for 27 adrenal cortical tumors, including aldosterone-producing adenomas (APA; n=8), cortisol-producing adenomas (CPA; n=11), and adrenal cortical carcinomas (ACC; n=8), highlighted known differentially-expressed genes (DEGs; i. e., CYP11B2, IGF2, etc.) and tumor type-specific transcriptional modules (i. e., high cell cycle/proliferation transcript expression in ACC, etc.), and a subset of DEGs was validated orthogonally using quantitative reverse transcription PCR (qRT-PCR). Finally, unsupervised hierarchical clustering using a subset of high-confidence DEGs revealed three discrete clusters representing APA, CPA, and ACC tumors with corresponding unique gene expression signatures, suggesting potential clinical utility for a transcriptomic-based approach to tumor classification. Overall, these data support the use of targeted amplicon-based RNAseq for comprehensive transcriptomic profiling of archival FFPE adrenal tumor material and indicate that this approach may facilitate important translational research opportunities for the study of these tumors.</jats:p>
収録刊行物
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- Hormone and Metabolic Research
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Hormone and Metabolic Research 52 (08), 607-613, 2020-08
Georg Thieme Verlag KG