Abundance of DLK1, differential expression of CYP11B1, CYP21A2 and MC2R, and lack of INSL3 distinguish testicular adrenal rest tumours from Leydig cell tumours

Lottrup, Grete; Nielsen, John; Skakkebæk, Niels E.; Juul, Anders; Meyts, Ewa Rajpert‐De

doi:10.1530/eje-14-0810

Cited by 40 publications

(16 citation statements)

References 30 publications

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“…For example, Rossato et al used the immunohistochemistry analysis to demonstrate that INSL3 expression was negative or decreased in Leydig cell tumor samples, but strongly and diffusely positive in normal Leydig cells and Leydig cell hyperplasia [31]. Lottrup et al also confirmed that INSL3 could not be detectable in testicular adrenal rest tumors [32]. Kaplan-Meier analysis of SNAP91 in the GSE7696 dataset showed that glioblastoma patients with high expression of SNAP91 exhibited a higher survival ratio compared with those having low levels of SNAP91 [33].…”

Section: Discussionmentioning

confidence: 99%

Identification of a Seven-lncRNA-mRNA Signature for Recurrence and Prognostic Prediction in Relapsed Acute Lymphoblastic Leukemia Based on WGCNA and LASSO Analyses

Chi

Wang

et al. 2021

Analytical Cellular Pathology

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Abnormal expressions of long noncoding RNAs (lncRNAs) and protein-encoding messenger RNAs (mRNAs) are important for the development of childhood acute lymphoblastic leukemia (ALL). This study developed an lncRNA-mRNA integrated classifier for the prediction of recurrence and prognosis in relapsed childhood ALL by using several transcriptome data. Weighted gene coexpression network analysis revealed that green, turquoise, yellow, and brown modules were preserved across the TARGET, GSE60926, GSE28460, and GSE17703 datasets, and they were associated with clinical relapse and death status. A total of 184 genes in these four modules were differentially expressed between recurrence and nonrecurrence samples. Least absolute shrinkage and selection operator analysis showed that seven genes constructed a prognostic signature (including one lncRNA: LINC00652 and six mRNAs: INSL3, NIPAL2, REN, RIMS2, RPRM, and SNAP91). Kaplan-Meier curve analysis observed that patients in the high-risk group had a significantly shorter overall survival than those of the low-risk group. Receiver operating characteristic curve analysis demonstrated that this signature had high accuracy in predicting the 5-year overall survival and recurrence outcomes, respectively. LINC00652 may function by coexpressing with the above prognostic genes (INSL3, SNAP91, and REN) and lipid metabolism-related genes (MIA2, APOA1). Accordingly, this lncRNA-mRNA-based classifier may be clinically useful to predict the recurrence and prognosis for childhood ALL. These genes represent new targets to explain the mechanisms for ALL.

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Section: Discussionmentioning

confidence: 99%

Identification of a Seven-lncRNA-mRNA Signature for Recurrence and Prognostic Prediction in Relapsed Acute Lymphoblastic Leukemia Based on WGCNA and LASSO Analyses

Chi

Wang

et al. 2021

Analytical Cellular Pathology

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“…Therefore, a clinical need for differential diagnostic markers that can differentiate between both pathologies exists. Bilateralism of the tumours ( 25 , 30 ), presence of Reinke crystals ( 1 , 5 , 25 , 31 , 31 , 32 , 33 , 34 ) and expressions of synaptophysin, Inhibin α, CD56, androgen receptor, DLK1, INSL3, CYP11B1, CYP21A2 and MC2R ( 33 , 34 , 35 , 36 ) have all been studied as potential markers, but none of these markers individually can reliably discriminate TARTs from LCTs. We found significantly higher gene expressions of GATA3 and GATA6 in TARTs compared to LCTs with good discriminative potential.…”

Section: Discussionmentioning

confidence: 99%

GATA transcription factors in testicular adrenal rest tumours

Engels

Span

Mitchell

et al. 2017

Endocrine Connections

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Testicular adrenal rest tumours (TARTs) are benign adrenal-like testicular tumours that frequently occur in male patients with congenital adrenal hyperplasia. Recently, GATA transcription factors have been linked to the development of TARTs in mice. The aim of our study was to determine GATA expression in human TARTs and other steroidogenic tissues. We determined GATA expression in TARTs (n = 16), Leydig cell tumours (LCTs; n = 7), adrenal (foetal (n = 6) + adult (n = 10)) and testis (foetal (n = 13) + adult (n = 8)). We found testis-like GATA4, and adrenal-like GATA3 and GATA6 gene expressions by qPCR in human TARTs, indicating mixed testicular and adrenal characteristics of TARTs. Currently, no marker is available to discriminate TARTs from LCTs, leading to misdiagnosis and incorrect treatment. GATA3 and GATA6 mRNAs exhibited excellent discriminative power (area under the curve of 0.908 and 0.816, respectively), while immunohistochemistry did not. GATA genes contain several CREB-binding sites and incubation with 0.1 mM dibutyryl cAMP for 4 h stimulated GATA3, GATA4 and GATA6 expressions in a human foetal testis cell line (hs181.tes). Incubation of adrenocortical cells (H295RA) with ACTH, however, did not induce GATA expression in vitro. Although ACTH did not dysregulate GATA expression in the only human ACTH-sensitive in vitro model available, our results do suggest that aberrant expression of GATA transcription factors in human TARTs might be involved in TART formation.

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“…CYP21A2, CYP11B1 and NR0B1/DAX1 mutations), the malignancy risk for the testis is estimated as being low (37,38,39). 46,XY patients with 21-hydroxylase deficiency and 11b-hydroxylase deficiency may develop TARTs, which can compromise fertility and sometimes be mistaken for Leydig cell malignancy; but TARTs are benign (37,40) and can be controlled by proper treatment (41). Importantly, testosterone overproduction as seen in some of these defects seems not to be associated with increased germ cell cancer risk (15,37).…”

Section: European Journal Of Endocrinologymentioning

confidence: 99%

Human 3β-hydroxysteroid dehydrogenase deficiency seems to affect fertility but may not harbor a tumor risk: lesson from an experiment of nature

Burckhardt

Udhane

Marti

et al. 2015

European Journal of Endocrinology

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Context: 3b-hydroxysteroid dehydrogenase deficiency (3bHSD) is a rare disorder of sexual development and steroidogenesis. There are two isozymes of 3bHSD, HSD3B1 and HSD3B2. Human mutations are known for the HSD3B2 gene which is expressed in the gonads and the adrenals. Little is known about testis histology, fertility and malignancy risk. Objective: To describe the molecular genetics, the steroid biochemistry, the (immuno-)histochemistry and the clinical implications of a loss-of-function HSD3B2 mutation. Methods: Biochemical, genetic and immunohistochemical investigations on human biomaterials. Results: A 46,XY boy presented at birth with severe undervirilization of the external genitalia. Steroid profiling showed low steroid production for mineralocorticoids, glucocorticoids and sex steroids with typical precursor metabolites for HSD3B2 deficiency. The genetic analysis of the HSD3B2 gene revealed a homozygous c.687del27 deletion. At pubertal age, he showed some virilization of the external genitalia and some sex steroid metabolites appeared likely through conversion of precursors secreted by the testis and converted by unaffected HSD3B1 in peripheral tissues. However, he also developed enlarged breasts through production of estrogens in the periphery. Testis histology in late puberty revealed primarily a Sertoli-cell-only pattern and only few tubules with arrested spermatogenesis, presence of few Leydig cells in stroma, but no neoplastic changes. Conclusions: The testis with HSD3B2 deficiency due to the c.687del27 deletion does not express the defective protein. This patient is unlikely to be fertile and his risk for gonadal malignancy is low. Further studies are needed to obtain firm knowledge on malignancy risk for gonads harboring defects of androgen biosynthesis.

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Abundance of DLK1, differential expression of CYP11B1, CYP21A2 and MC2R, and lack of INSL3 distinguish testicular adrenal rest tumours from Leydig cell tumours

Cited by 40 publications

References 30 publications

Identification of a Seven-lncRNA-mRNA Signature for Recurrence and Prognostic Prediction in Relapsed Acute Lymphoblastic Leukemia Based on WGCNA and LASSO Analyses

Identification of a Seven-lncRNA-mRNA Signature for Recurrence and Prognostic Prediction in Relapsed Acute Lymphoblastic Leukemia Based on WGCNA and LASSO Analyses

GATA transcription factors in testicular adrenal rest tumours

Human 3β-hydroxysteroid dehydrogenase deficiency seems to affect fertility but may not harbor a tumor risk: lesson from an experiment of nature

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