Molecular genetics of adrenocortical tumours, from familial to sporadic diseases

Libé, Rossella; Bertherat, Jérôme

doi:10.1530/eje.1.02004

Cited by 168Adrenal and Paraganglionic TumorsAdrenal Hormones and DisordersChromatin Remodeling and Cancer

Molecular genetics of adrenocortical tumours, from familial to sporadic diseases

Libé, Rossella, Bertherat, Jérôme·2005·European Journal of Endocrinology

DOI 10.1530/eje.1.02004

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Abstract

Adrenal masses can be detected in up to 4% of the population, and are mostly of adrenocortical origin. Adrenocortical tumours (ACTs) may be responsible for excess steroid production and, in the case of adrenocortical cancers, for morbidity or mortality due to tumour growth. Our understanding of the pathogenesis of ACTs is more limited than that for other tumours. However, studies of the genetics of ACTs have led to major advances in this field in the last decade. The identification of germline molecular defects in the hereditary syndrome responsible for ACTs has facilitated progress. Indeed, similar molecular defects have since been identified as somatic alterations in sporadic tumours. The familial diseases concerned are Li-Fraumeni syndrome, which may be due to germline mutation of the tumour-suppressor gene TP53 and Beckwith-Wiedemann syndrome, which is caused by dys-regulation of the imprinted IGF-II locus at 11p15. ACTs also occur in type 1 multiple endocrine neoplasia (MEN 1), which is characterized by a germline mutation of the menin gene. Cushing's syndrome due to primary pigmented nodular adrenocortical disease (PPNAD) has been observed in Carney complex patients presenting inactivating germline PRKAR1A mutations. Interestingly, allelic losses at 17p13 and 11p15 have been demonstrated in sporadic adrenocortical cancer and somatic PRKAR1A mutations have been found in secreting adrenocortical adenomas. More rarely, mutations in Gs protein (gsp) and the gene for ACTH receptor have been observed in ACTs. The genetics of another group of adrenal diseases that can lead to adrenal nodular hyperplasia -- congenital adrenal hyperplasia (CAH) and glucocorticoid-remediable aldosteronism (GRA) -- have also been studied extensively. This review summarizes recent advances in the genetics of ACTs, highlighting both improvements in our understanding of the pathophysiology and the diagnosis of these tumours.

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Perturbation of the IGF2 locus, with upregulation of IGF2 and downregulation of H19 and CDKN1C, is frequently observed in ACCs.
“Perturbation of the IGF2 locus, with upregulation of maternally imprinted genes (IGF2), and downregulation of paternally imprinted genes (H19 and CDKN1C), is frequently observed in ACCs (226).”
From Adrenocortical carcinoma (2014) · cites this paper as [226]

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MEN1 Gene Analysis in Sporadic Adrenocortical Neoplasms
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Are activating mutations of the adrenocorticotropin receptor involved in adrenal cortical neoplasia?
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Deletion of the Adrenocorticotropin Receptor Gene in Human Adrenocortical Tumors: Implications for Tumorigenesis
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Ribonucleic Acid Expression of the Clustered Imprinted Genes, p57KIP2, Insulin-Like Growth Factor II, and H19, in Adrenal Tumors and Cultured Adrenal Cells1
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Recent advances in the pathogenesis of adrenocortical tumours
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Loss of Expression of the Ubiquitous Transcription Factor cAMP Response Element-Binding Protein (CREB) and Compensatory Overexpression of the Activator CREM in the Human Adrenocortical Cancer Cell Line H295R
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Genotyping of Adrenocortical Tumors: Very Frequent Deletions of the MEN1 Locus in 11q13 and of a 1-Centimorgan Region in 2p16
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A Case Report in Favor of a Multistep Adrenocortical Tumorigenesis
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Adrenal incidentalomas
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Mutations of the p53 gene in human functional adrenal neoplasms
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New Genetic Insights in Familial Hyperaldosteronism
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Steroid 21-Hydroxylase Mutations and 21-Hydroxylase Messenger Ribonucleic Acid Expression in Human Adrenocortical Tumors
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Complete Sequencing and Messenger Ribonucleic Acid Expression Analysis of the MEN I Gene in Adrenal Cancer1
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Assessing the Presence of Abnormal Regulation of Cortisol Secretion by Membrane Hormone Receptors:In VivoandIn VitroStudies in Patients with Functioning and Non-functioning Adrenal Adenoma
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p53 mutations in adrenal tumors: Caucasian patients do not show the exon 4 "hot spot" found in Taiwan
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Complete Sequencing and Messenger Ribonucleic Acid Expression Analysis of the MEN I Gene in Adrenal Cancer
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Transforming Growth Factor ß1: An Autocrine Regulator of Adrenocortical Steroidogenesis
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Fibroblast Growth Factor-2 Inhibits the Maturation of Pro-Insulin-Like Growth Factor-II (Pro-IGF-II) and the Expression of Insulin-Like Growth Factor Binding Protein-2 (IGFBP-2) in the Human Adrenocortical Tumor Cell Line NCI-H295R
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Computed tomography in untreated adults with virilising congenital adrenal cortical hyperplasia
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Pituitary Tumour Clonality Revisited
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Ribonucleic Acid Expression of the Clustered Imprinted Genes, p57KIP2, Insulin-Like Growth Factor II, and H19, in Adrenal Tumors and Cultured Adrenal Cells
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Increased prevalence of heterozygous 21‐OH germline mutations in patients with adrenal incidentalomas
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Metabolism of glucocorticoids and mineralocorticoids in patients with adrenal incidentalomas
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Late relapse of adrenocortical carcinoma in Beckwith‐Wiedemann syndrome. Clinical, endocrinological and genetic aspects
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[Aberrant expression of the GIP (Gastric Inhibitory Polypeptide) receptor in an adrenal cortical adenoma responsible for a case of food-dependent Cushing's syndrome].
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Adrenal Lymphocytic Infiltration and Adrenocortical Tumors in a Patient with 21-Hydroxylase Deficiency
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Transcription Factor 3′,5′-Cyclic Adenosine 5′-Monophosphate-Responsive Element-Binding Protein (CREB) Is Decreased during Human Adrenal Cortex Tumorigenesis and Fetal Development
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Mapping the Human Melanocortin 2 Receptor (Adrenocorticotropic Hormone Receptor; ACTHR) Gene (MC2R) to the Small Arm of Chromosome 18 (18p11.21-pter)
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No overrepresentation of congenital adrenal hyperplasia in patients with adrenocortical tumours
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Variable Expression of the Transcription Factors cAMP Response Element-Binding Protein and Inducible cAMP Early Repressor in the Normal Adrenal Cortex and in Adrenocortical Adenomas and Carcinomas
Peri, A., Luciani, P., Conforti, B., Baglioni-Peri, S., Cioppi, F., Crescioli, C., Ferruzzi, P., Gelmini, S., Arnaldi, G., Nesi, G., et al. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.11.8042 · Cited by 26 · see citing works
Gastric inhibitory polypeptide (GIP) stimulates cortisol secretion, cAMP production and DNA synthesis in an adrenal adenoma responsible for food-dependent cushing's syndrome.
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Human ACTH hypersensitivity syndrome associated with abnormalities of the ACTH receptor gene
Hiroi, N., Yakushiji, F., Shimojo, M., Watanabe, S., Sugano, S., Yamaguchi, N., & Miyachi, Y. (1998) · Clinical Endocrinology · doi:10.1046/j.1365-2265.1998.3971187.x · Cited by 24 · see citing works
Beckwith-Wiedemann syndrome and virilizing cortical adrenal tumor in a child
Sbragia-Neto, L., Filho, A. A. M., Guerra‐Júnior, G., de Lemos‐Marini, S. H. V., Baptista, M. T. M., de Matos, P. S., de Oliveira-Filho, A. G., & Bustorff‐Silva, J. M. (2000) · Journal of Pediatric Surgery · doi:10.1053/jpsu.2000.8771 · Cited by 20 · see citing works
Concurrent translocations ofMLL andCBFA2 (AML1) genes with new partner breakpoints in a child with secondary myelodysplastic syndrome after treatment of acute lymphoblastic leukemia
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Protein kinase A in Carney complex: a new example of cAMP pathway alteration in endocrine tumors
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[Hyperaldosteronism sensitive to dexamethasone with adrenal adenoma. Clinical, biological and genetic study].
Jeunemaı̂tre, X., Charru, A., Pascoe, L., Guyene, T. T., Aupetit, B., Shackleton, C. H. L., Schambelan, M., Plouin, P., & Corvol, P. L. (1995) · PubMed · Cited by 10 · see citing works
Molecular biology of human pituitary adenomas
Farrell, W. E., & Clayton, R. N. (1998) · Annals of Medicine · doi:10.3109/07853899808999403 · Cited by 9 · see citing works

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Adrenocortical carcinoma
Else, T., Kim, A. C., Sabolch, A., Raymond, V. M., Kandathil, A., Caoili, E. M., Jolly, S., Miller, B. S., Giordano, T. J., & Hammer, G. D. (2014) · Endocrine Reviews · doi:10.1210/er.2013-1029 · Cited by 892 · see citing works
Adrenocortical Carcinoma: Clinical Update
Allolio, B., & Fassnacht, M. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-2639 · Cited by 775 · see citing works
Beyond Li Fraumeni Syndrome: Clinical Characteristics of Families With p53 Germline Mutations
Hagman, K. D. F., Noltner, K., Buzin, C. H., Gu, D., Wen, C. Y., Nguyen, V. Q., Han, J., Lowstuter, K. J., Longmate, J., Sommer, S. S., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.16.6959 · Cited by 607 · see citing works
A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment
Hampel, H., Bennett, R. L., Buchanan, A. H., Pearlman, R., & Wiesner, G. L. (2014) · Genetics in Medicine · doi:10.1038/gim.2014.147 · Cited by 590 · see citing works
Clinical and biological features in the prognosis of adrenocortical cancer: poor outcome of cortisol-secreting tumors in a series of 202 consecutive patients
Abiven, G., Coste, J., Groussin, L., Anract, P., Tissier, F., Legmann, P., Dousset, B., Bertagna, X., & Bertherat, J. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-2730 · Cited by 435 · see citing works
Self-citation
Molecular classification and prognostication of adrenocortical tumors by transcriptome profiling
Giordano, T. J., Kuick, R., Else, T., Gauger, P. G., Vinco, M., Bauersfeld, J., Sanders, D., Thomas, D. G., Doherty, G., & Hammer, G. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-1067 · Cited by 401 · see citing works
Clinical management of adrenocortical carcinoma
Fassnacht, M., & Allolio, B. (2009) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2008.10.008 · Cited by 349 · see citing works
Menin: a scaffold protein that controls gene expression and cell signaling
Matkar, S. S., Thiel, A. T., & Hua, X. (2013) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2013.05.005 · Cited by 295 · see citing works
Adrenocortical cancer: pathophysiology and clinical management
Libé, R., Fratticci, A., & Bertherat, J. Y. (2007) · Endocrine Related Cancer · doi:10.1677/erc.1.01130 · Cited by 271 · see citing works
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Adrenal Imaging
Blake, M. A., Cronin, C. G., & Boland, G. W. (2010) · American Journal of Roentgenology · doi:10.2214/ajr.10.4547 · Cited by 254 · see citing works
The Weiss system for evaluating adrenocortical neoplasms: 25 years later
Lau, S. K., & Weiss, L. M. (2009) · Human Pathology · doi:10.1016/j.humpath.2009.03.010 · Cited by 223 · see citing works
Wnt/β-catenin and 3′,5′-cyclic adenosine 5′-monophosphate/protein kinase A signaling pathways alterations and somatic β-catenin gene mutations in the progression of adrenocortical tumors
Gaujoux, S., Tissier, F., Groussin, L., Libé, R., Ragazzon, B., Launay, P., Audebourg, A., Dousset, B., Bertagna, X., & Bertherat, J. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-0631 · Cited by 142 · see citing works
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Childhood adrenocortical tumours
Ribeiro, R. C., & de Figueiredo, B. C. (2004) · European Journal of Cancer · doi:10.1016/j.ejca.2004.01.031 · Cited by 140 · see citing works
Genetics of adrenal tumors associated with Cushing's syndrome: a new classification for bilateral adrenocortical hyperplasias
Stratakis, C. A., & Boikos, S. A. (2007) · Nature Clinical Practice Endocrinology &#38 Metabolism · doi:10.1038/ncpendmet0648 · Cited by 129 · see citing works
Wnt/β-catenin signalling in adrenal physiology and tumour development
Berthon, A., Martinez, A., Bertherat, J., & Val, P. (2012) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2011.09.009 · Cited by 125 · see citing works
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Phosphodiesterase 11A (PDE11A) and Genetic Predisposition to Adrenocortical Tumors
Libé, R., Fratticci, A., Coste, J., Tissier, F., Horvath, A., Ragazzon, B., René-Corail, F., Groussin, L., BERTAGNA, X. Y., Raffin‐Sanson, M. L., et al. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-0106 · Cited by 124 · see citing works
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Li‐Fraumeni syndrome: a paradigm for the understanding of hereditary cancer predisposition
Valdez, J. M., Nichols, K. E., & Kesserwan, C. A. (2016) · British Journal of Haematology · doi:10.1111/bjh.14461 · Cited by 121 · see citing works
Somatic TP53 Mutations Are Relatively Rare among Adrenocortical Cancers with the Frequent 17p13 Loss of Heterozygosity
Libè, R., Groussin, L., Tissier, F., Elie, C., René-Corail, F., Fratticci, A., Jullian, E., Beck-Peccoz, P., Bertagna, X., Gicquel, C., et al. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-2085 · Cited by 115 · see citing works
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Large Deletions of the PRKAR1A Gene in Carney Complex
Horvath, A., Bossis, I., Giatzakis, C., Levine, E., Weinberg, F. D., Meoli, E., Robinson-White, A. J., Siegel, J., Soni, P., Groussin, L., et al. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-1155 · Cited by 106 · see citing works
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Menin Epigenetically Represses Hedgehog Signaling in MEN1 Tumor Syndrome
Gurung, B., Feng, Z., Iwamoto, D. V., Thiel, A. T., Jin, G., Fan, C.-M., Ng, J. M. Y., Curran, T., & Hua, X. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-3158 · Cited by 101 · see citing works
Current management of adrenal tumors
Kuruba, R., & Gallagher, S. F. (2008) · Current Opinion in Oncology · doi:10.1097/cco.0b013e3282f301fd · Cited by 85 · see citing works
Genetics of tumors of the adrenal cortex
Bonnet-Serrano, F., & Bertherat, J. (2018) · Endocrine Related Cancer · doi:10.1530/erc-17-0361 · Cited by 80 · see citing works
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Role of the Insulin-like Growth Factor System in Adrenocortical Growth Control and Carcinogenesis
Fottner, C., Hoeflich, A., Wolf, E., & Weber, M. (2004) · Hormone and Metabolic Research · doi:10.1055/s-2004-814563 · Cited by 78 · see citing works
Transcriptional profiling enables molecular classification of adrenocortical tumours
Laurell, C., Velázquez‐Fernández, D., Lindsten, K., Juhlin, C. C., Enberg, U., Geli, J., Höög, A., Kjellman, M., Lundeberg, J., Hamberger, B., et al. (2009) · European Journal of Endocrinology · doi:10.1530/eje-09-0068 · Cited by 77 · see citing works
Adrenocortical carcinoma: The management of metastatic disease
Fay, A. P., Elfiky, A. A., Teló, G. H., McKay, R. R., Kaymakcalan, M. D., Nguyen, P. L., Vaidya, A., Ruan, D. T., Joaquim Bellmunt, B., & Choueiri, T. K. (2014) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2014.05.009 · Cited by 69 · see citing works
Update on tumours of the adrenal cortex, phaeochromocytoma and extra‐adrenal paraganglioma
McNicol, A. M. (2010) · Histopathology · doi:10.1111/j.1365-2559.2010.03613.x · Cited by 68 · see citing works
REVIEW PAPER: Origin and Molecular Pathology of Adrenocortical Neoplasms
Bielińska, M., Parviainen, H., Kiiveri, S., Heikinheimo, M., & Wilson, D. B. (2009) · Veterinary Pathology · doi:10.1354/vp.08-vp-0179-w-rev · Cited by 67 · see citing works
Expression of progesterone and estradiol receptors in normal adrenal cortex, adrenocortical tumors, and primary pigmented nodular adrenocortical disease
de Crémoux, P., Rosenberg, D., Goussard, J., Brémont-Weil, C., Tissier, F., Tran‐Perennou, C., Groussin, L., BERTAGNA, X. Y., Bertherat, J. Y., & Raffin‐Sanson, M. (2008) · Endocrine Related Cancer · doi:10.1677/erc-07-0081 · Cited by 63 · see citing works
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The molecular genetics of adrenocortical carcinoma
Barlaskar, F. M., & Hammer, G. D. (2007) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-007-9057-x · Cited by 56 · see citing works
Ghrelin and its unacylated isoform stimulate the growth of adrenocortical tumor cells via an anti-apoptotic pathway
Delhanty, P. J. D., van Koetsveld, P. M., Gauna, C., van de Zande, B., Vitale, G., Hofland, L. J., & van der Lely, A. J. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00377.2006 · Cited by 55 · see citing works
Epidermal growth factor receptor in adrenocortical tumors: analysis of gene sequence, protein expression and correlation with clinical outcome
Adam, P., Hahner, S., Hartmann, M., Heinrich, B., Quinkler, M. O., Willenberg, H. S., Saeger, W., Sbiera, S., Schmull, S., Voelker, H.-U., et al. (2010) · Modern Pathology · doi:10.1038/modpathol.2010.153 · Cited by 54 · see citing works
Pathogenesis of adrenocortical cancer
Bertherat, J. Y., & BERTAGNA, X. Y. (2009) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2008.10.006 · Cited by 55 · see citing works
Self-citation
Adrenocortical tumors and hyperplasias in childhood--etiology, genetics, clinical presentation and therapy.
Sutter, J. A., & Grimberg, A. (2006) · PubMed · Cited by 51 · see citing works
GENETICS IN ENDOCRINOLOGY: Glucocorticoid resistance syndrome
Vitellius, G., & Lombès, M. (2019) · European Journal of Endocrinology · doi:10.1530/eje-19-0811 · Cited by 49 · see citing works
Preoperative 18F‐FDG Uptake is Strongly Correlated with Malignancy, Weiss Score, and Molecular Markers of Aggressiveness in Adrenal Cortical Tumors
Gust, L., Taïeb, D., Beliard, A., Barlier, A., Morange, I., Micco, C. D., Henry, J., & Sebag, F. A. (2011) · World Journal of Surgery · doi:10.1007/s00268-011-1374-2 · Cited by 48 · see citing works
The role of mTOR inhibitors in the inhibition of growth and cortisol secretion in human adrenocortical carcinoma cells
Martino, M. C. D., van Koetsveld, P. M., Feelders, R. A., Sprij-Mooij, D. M., Waaijers, M., Lamberts, S. W. J., de Herder, W. W., Colao, A., Pivonello, R., & Hofland, L. J. (2012) · Endocrine Related Cancer · doi:10.1530/erc-11-0270 · Cited by 48 · see citing works
Menin Directly Represses Gli1 Expression Independent of Canonical Hedgehog Signaling
Gurung, B., Feng, Z., & Hua, X. (2013) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-13-0170 · Cited by 46 · see citing works
Clinical impact of TP53 alterations in adrenocortical carcinomas
Waldmann, J., Patsalis, N., Fendrich, V., Langer, P., Saeger, W., Chaloupka, B., Ramaswamy, A., Faßnacht, M., Bartsch, D. K., & Slater, E. P. (2011) · Langenbeck s Archives of Surgery · doi:10.1007/s00423-011-0868-6 · Cited by 45 · see citing works
The pathophysiology, diagnosis and prognosis of adrenocortical tumors revisited by transcriptome analyses
Assié, G., Guillaud-Bataille, M., Ragazzon, B., BERTAGNA, X. Y., Bertherat, J. Y., & Clauser, É. (2010) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2009.12.009 · Cited by 43 · see citing works
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P53/Rb inhibition induces metastatic adrenocortical carcinomas in a preclinical transgenic model
Batisse‐Lignier, M., Sahut‐Barnola, I., Tissier, F., Dumontet, T., Mathieu, M., Drelon, C., Pointud, J.-C., Damon‐Soubeyrand, C., Marceau, G., Kemeny, J.-L., et al. (2017) · Oncogene · doi:10.1038/onc.2017.54 · Cited by 42 · see citing works
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The Genetics of Adrenocortical Tumors
Espiard, S., & Bertherat, J. Y. (2015) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2015.02.004 · Cited by 42 · see citing works
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Gene expression profiling in adrenocortical neoplasia
Assié, G., Giordano, T. J., & Bertherat, J. Y. (2011) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2011.09.044 · Cited by 41 · see citing works
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Li–Fraumeni syndrome heterogeneity
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REVIEW Molecular genetics of adrenocortical tumours, from familial to sporadic diseases
Libé, R., & Bertherat, J. Y. (2013)
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Authors: Libé, R., & Bertherat, J.
Venue: European Journal of Endocrinology
Publisher: Oxford University Press (OUP)
Published: 2005-10
Volume: 153
Issue: 4
Pages: 477-487
ISSN: 0804-4643 (ISSN-L)
1479-683X
DOI: 10.1530/eje.1.02004
OpenAlex: W2171162119
Cited by: 168
References: 106
Citations by year: 2025: 1 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 4 · 2020: 3 · 2019: 6 · 2018: 8 · 2017: 5 · 2016: 8 · 2015: 11 · 2014: 14 · 2013: 6 · 2012: 13
FWCI: 2.36
Type: journal article
Language: en
Open access: closed
Locations: European Journal of Endocrinology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Keywords: adrenocortical tumors, adrenocortical carcinoma, adrenal adenoma, Li-Fraumeni syndrome, TP53, Beckwith-Wiedemann syndrome, multiple endocrine neoplasia type 1, Carney complex, PRKAR1A mutation, Cushing's syndrome, primary pigmented nodular adrenocortical disease, loss of heterozygosity, 17p13, 11p15, ACTH receptor, adrenal nodular hyperplasia, congenital adrenal hyperplasia, glucocorticoid-remediable aldosteronism, hereditary cancer, somatic mutations
MeSH terms: Adrenal Cortex Neoplasms, Humans, Molecular Biology

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Molecular genetics of adrenocortical tumours, from familial to sporadic diseases

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