Adrenocortical carcinoma is characterized by a high frequency of chromosomal gains and high‐level amplifications

Dohna, Martha; Reincke, Martín; Mincheva, Antoaneta; Allolio, Bruno; Solinas‐Toldo, Sabina; Lichter, Peter

doi:10.1002/(sici)1098-2264(200006)28:2<145::aid-gcc3>3.3.co;2-z

Cited by 26 publications

(42 citation statements)

References 20 publications

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“…The occurrence of an adrenocortical carcinoma in our patient with isolated LIT1 hypomethylation supports the observations by Weksberg et al Future increased knowledge about the genetic basis of BWS and genotype phenotype correlations may be of importance for planning clinical control in patients suspected of having BWS. The karyotype of the metastasis revealed a complex pattern in accordance with other reports on the karyotype in primary adrenocortical carcinoma (15). However, no aberration of chromosome 11p15 was encountered in the metastasis, as has been described for adrenocortical carcinomas (16).…”

Section: Discussionsupporting

confidence: 89%

Late relapse of adrenocortical carcinoma in Beckwith‐Wiedemann syndrome. Clinical, endocrinological and genetic aspects

et al. 2003

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We report on a girl with an unusual Beckwith‐Wiedemann syndrome (BWS) and hemihypertrophy, who developed an adrenocortical carcinoma with atypical clinical behaviour. At 4 y of age the girls was admitted to hospital with cushingoid features, virilization, increased excretion of steroids and low serum ACTH. A right‐sided adrenocortical carcinoma was removed. At age 12.5 y the cushingoid features reappeared together with a tumour in the left thigh. A CT scan of the thorax and abdomen revealed pulmonary metastasis only. Corticosteroid excretion was increased and serum ACTH level suppressed. The femoral and the pulmonary metastases were removed and histology showed adrenocortical carcinoma. Excretion of corticosteroids subsequently normalized. Meningeal and pulmonary metastases with similar histologies appeared one year later with normal hormone values. Twenty‐two months after the recurrence the girl died of an intracranial metastasis. Southern blot analysis of the LIT1 transcript in the KvLQT1 gene in the BWS region on chromosome 11p15 revealed hypomethylation of the maternal allele. Conclusion: Adrenocortical carcinoma in childhood may recur years after onset and at rare sites and hormonal levels may be an insufficient indicator of small metastases.

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Section: Discussionsupporting

confidence: 89%

Late relapse of adrenocortical carcinoma in Beckwith‐Wiedemann syndrome. Clinical, endocrinological and genetic aspects

et al. 2003

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“…Losses most often involved the chromosomal regions 2, 11q and 17p, whereas gains took place at chromosomes 4 and 5. These results differ from our own experience using CGH in seven adenomas and 14 carcinomas [30]. Chromosomal gains were much more prevalent than losses and affected chromosomes 16p, 20q (each 11/14 tumours), 5, 7, 9q, 12q, 14q (each 7/14 tumours).…”

Section: Cytogenetic Aspects Of Adrenocortical Tumourigenesiscontrasting

confidence: 97%

Molecular adrenocortical tumourigenesis

Reincke

Beuschlein

Slawik

et al. 2000

Eur J Clin Investigation

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Adrenocortical neoplasms are the most frequent abnormality of the adrenal cortex. Most of these lesions are clinically silent and are detected incidentally by ultrasound or computed tomography. The prevalence of these so-called 'incidentalomas' in the general population is around 1%, increasing with age and reaching 6% among those in the age range 60-70 years. In contrast, primary adrenocortical carcinoma, a highly malignant tumour, is rare, having an incidence of one case per million per year. Recent progress has been achieved in the understanding of adrenocortical tumourigenesis by mapping and identification of genes responsible for hereditary tumours that involve the adrenal gland. Investigation of the clonal composition of adrenal tumours demonstrates that adrenal carcinomas are monoclonal, whereas adrenal adenoma may be polyclonal in approximately 25-40% of cases. Oncogenes and tumour-suppressor genes involved in adrenal carcinomas include mutations in the p53 tumour-suppressor gene and rearrangements of the chromosomal locus 11p15.5 associated with IGF II hyperexpression. Constitutive activation of the ACTH receptor-G protein-cAMP signal cascade does not play a role in adrenal tumour formation. Conversely, deletions of the ACTH receptor gene have recently been found in undifferentiated adenomas and in aggressive adrenocortical carcinomas, and, more recently, confirmed in a larger series of tumours. The available literature indicates that the signalling pathways of adrenocortical tumours are different from those of other endocrine neoplasms, such as pituitary and thyroid adenomas.

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“…Interestingly, amplification of the 11q13 chromosomal region which carries PDE2A gene occurs in several human cancers including ACCs. 41 In addition, PDE2A has been shown to be overexpressed in ACC mutated for b-catenin gene CTNNB1. 42 Whether the expression of miR-139-5p is correlated with or independent from that of its host gene PDE2A in ACC remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

MiR‐483‐5p and miR‐139‐5p promote aggressiveness by targeting N‐myc downstream‐regulated gene family members in adrenocortical cancer

Agosta

Laugier

Guyon

et al. 2018

Intl Journal of Cancer

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Adrenocortical carcinoma (ACC) is a tumor with poor prognosis in which overexpression of a panel of microRNAs has been associated with malignancy but a very limited number of investigations on their role in ACC pathogenesis have been conducted. We examined the involvement of miR-483-5p and miR-139-5p in adrenocortical cancer aggressiveness. Using bioinformatics predictions and mRNA/miRNA expression profiles, we performed an integrated analysis to identify inversely correlated miRNA-mRNA pairs in ACC. We identified N-myc downstream-regulated gene family members 2 and 4 (NDRG2 and NDRG4) as targets of miR-483-5p and miR-139-5p, respectively. NDRG2 and NDRG4 expressions were inversely correlated respectively with miR-483-5p and miR-139-5p levels in aggressive ACC samples from two independent cohorts of 20 and 44 ACC. Moreover, upregulation of miR-139-5p and downregulation of NDRG4 demonstrated a striking prognostic value. A direct interaction between miR-483-5p or miR-139-5p and their targets was demonstrated in reporter assays. Downregulation of miR-483-5p or miR-139-5p in the ACC cell lines NCI-H295R and SW13 increased NDRG2 or NDRG4 mRNA and protein expression, compromised adrenocortical cancer cell invasiveness and anchorage-independent growth. MiR-483-5p or miR-139-5p overexpression and NDRG2 or NDRG4 inhibition produce similar changes, which are rescued by NDRG2 or NDRG4 ectopic expression. We established that key factors mediating epithelial-to-mesenchymal transition are downstream effectors of miR-483-5p/NDRG2 and miR-139-5p/NDRG4 pathways. Collectively, our data show for the first time that miR-483-5p/NDRG2 and miR-139-5p/NDRG4 axes promote ACC aggressiveness, with potential implications for prognosis and therapeutic interventions in adrenocortical malignancies.

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Adrenocortical carcinoma is characterized by a high frequency of chromosomal gains and high‐level amplifications

Cited by 26 publications

References 20 publications

Late relapse of adrenocortical carcinoma in Beckwith‐Wiedemann syndrome. Clinical, endocrinological and genetic aspects

Late relapse of adrenocortical carcinoma in Beckwith‐Wiedemann syndrome. Clinical, endocrinological and genetic aspects

Molecular adrenocortical tumourigenesis

MiR‐483‐5p and miR‐139‐5p promote aggressiveness by targeting N‐myc downstream‐regulated gene family members in adrenocortical cancer

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