In:
Hormone and Metabolic Research, Georg Thieme Verlag KG, Vol. 52, No. 08 ( 2020-08), p. 607-613
Kurzfassung:
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.
Materialart:
Online-Ressource
ISSN:
0018-5043
,
1439-4286
Sprache:
Englisch
Verlag:
Georg Thieme Verlag KG
Publikationsdatum:
2020
ZDB Id:
2056576-8
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