RNA Sequencing and Somatic Mutation Status of Adrenocortical Tumors: Novel Pathogenetic Insights.
J Clin Endocrinol Metab
; 105(12)2020 12 01.
Article
em En
| MEDLINE
| ID: mdl-32875319
ABSTRACT
CONTEXT Pathogenesis of autonomous steroid secretion and adrenocortical tumorigenesis remains partially obscure. OBJECTIVE:
To investigate the relationship between transcriptome profile and genetic background in a large series of adrenocortical tumors and identify new potential pathogenetic mechanisms.DESIGN:
Cross-sectional study.SETTING:
University Hospitals of the European Network for the Study of Adrenal Tumors (ENSAT). PATIENTS We collected snap-frozen tissue from patients with adrenocortical tumors (n = 59) with known geneticbackground:
26 adenomas with Cushing syndrome (CS- cortisol-producing adenoma [CPA]), 17 adenomas with mild autonomous cortisol secretion (MACS-CPAs), 9 endocrine-inactive adenomas (EIAs), and 7 adrenocortical carcinomas (ACCs). INTERVENTION Ribonucleic acid (RNA) sequencing. MAIN OUTCOMEMEASURES:
Gene expression, long noncoding RNA (lncRNA) expression, and gene fusions. Correlation with genetic background defined by targeted Sanger sequencing, targeted panel- or whole-exome sequencing.RESULTS:
Transcriptome analysis identified 2 major clusters for adenomas Cluster 1 (n = 32) mainly consisting of MACS-CPAs with CTNNB1 or without identified driver mutations (46.9% of cases) and 8/9 EIAs; Cluster 2 (n = 18) that comprised CP-CPAs with or without identified driver mutation in 83.3% of cases (including all CS-CPAs with PRKACA mutation). Two CS-CPAs, 1 with CTNNB1 and 1 with GNAS mutation, clustered separately and relatively close to ACC. lncRNA analysis well differentiate adenomas from ACCs. Novel gene fusions were found, including AKAP13-PDE8A in one CS-CPA sample with no driver mutation.CONCLUSIONS:
MACS-CPAs and EIAs showed a similar transcriptome profile, independently of the genetic background, whereas most CS-CPAs clustered together. Still unrevealed molecular alterations in the cAMP/PKA or Wnt/beta catenin pathways might be involved in the pathogenesis of adrenocortical tumors.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias do Córtex Suprarrenal
/
Adenoma Adrenocortical
Tipo de estudo:
Observational_studies
/
Prevalence_studies
/
Risk_factors_studies
Limite:
Aged
/
Female
/
Humans
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Male
/
Middle aged
País/Região como assunto:
Europa
Idioma:
En
Revista:
J Clin Endocrinol Metab
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Itália