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Combined steroidogenic characters of fetal adrenal and Leydig cells in childhood adrenocortical carcinoma
- Source :
- The Journal of steroid biochemistry and molecular biology. 159
- Publication Year :
- 2015
-
Abstract
- Although childhood adrenocortical carcinomas (c-ACCs) with a TP53 mutation are known to produce androgens, detailed steroidogenic characters have not been clarified. Here, we examined steroid metabolite profiles and expression patterns of steroidogenic genes in a c-ACC removed from the left adrenal position of a 2-year-old Brazilian boy with precocious puberty, using an atrophic left adrenal gland removed at the time of tumorectomy as a control. The c-ACC produced not only abundant dehydroepiandrosterone-sulfate but also a large amount of testosterone via the Δ5 pathway with Δ5-androstenediol rather than Δ4-androstenedione as the primary intermediate metabolite. Furthermore, the c-ACC was associated with elevated expressions of CYP11A1, CYP17A1, POR, HSD17B3, and SULT2A1, a low but similar expression of CYB5A, and reduced expressions of AKR1C3 (HSD17B5) and HSD3B2. Notably, a Leydig cell marker INSL3 was expressed at a low but detectable level in the c-ACC. Furthermore, molecular studies revealed a maternally inherited heterozygous germline TP53 mutation, and several post-zygotic genetic aberrations in the c-ACC including loss of paternally derived chromosome 17 with a wildtype TP53 and loss of maternally inherited chromosome 11 and resultant marked hyperexpression of paternally expressed growth promoting gene IGF2 and drastic hypoexpression of maternally expressed growth suppressing gene CDKN1C. These results imply the presence of combined steroidogenic properties of fetal adrenal and Leydig cells in this patient's c-ACC with a germline TP53 mutation and several postzygotic carcinogenic events.
- Subjects :
- 0301 basic medicine
Male
medicine.medical_specialty
Endocrinology, Diabetes and Metabolism
Clinical Biochemistry
DNA Mutational Analysis
Gene Expression
Biology
Biochemistry
Germline
03 medical and health sciences
0302 clinical medicine
Endocrinology
Internal medicine
Cell Line, Tumor
Adrenal Glands
medicine
Adrenocortical Carcinoma
Biomarkers, Tumor
Adrenocortical carcinoma
Humans
Insulin
Cholesterol Side-Chain Cleavage Enzyme
Molecular Biology
Testosterone
Germ-Line Mutation
Comparative Genomic Hybridization
Leydig cell
Base Sequence
Cholesterol side-chain cleavage enzyme
Leydig Cells
Proteins
Steroid 17-alpha-Hydroxylase
Cell Biology
medicine.disease
Lipid Metabolism
Adrenal Cortex Neoplasms
Biosynthetic Pathways
Pedigree
Chromosome 17 (human)
030104 developmental biology
medicine.anatomical_structure
CYP17A1
030220 oncology & carcinogenesis
Child, Preschool
HSD3B2
Molecular Medicine
Tumor Suppressor Protein p53
Subjects
Details
- ISSN :
- 18791220
- Volume :
- 159
- Database :
- OpenAIRE
- Journal :
- The Journal of steroid biochemistry and molecular biology
- Accession number :
- edsair.doi.dedup.....91e624fdf923f9f427f66c974284d54a