Genomic classification of benign adrenocortical lesions

in Endocrine-Related Cancer
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  • 1 Université de Paris, Institut Cochin, INSERM, CNRS, Paris, France
  • 2 Department of Pathology, AP-HP, Hôpital Pitié-Salpétrière, Pierre et Marie Curie Université, Paris, France
  • 3 Department of Endocrinology, Center for Rare Adrenal Diseases, AP-HP, Hôpital Cochin, Paris, France
  • 4 Department of Hormonology, AP-HP, Hôpital Cochin, Paris, France
  • 5 Department of Endocrine Surgery, AP-HP, Hôpital Cochin, Paris, France
  • 6 Programme Cartes d’Identité des Tumeurs (CIT), Ligue Nationale Contre Le Cancer, Paris, France

Correspondence should be addressed to G Assié: guillaume.assie@inserm.fr
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Benign adrenal tumors cover a spectrum of lesions with distinct morphology and steroid secretion. Current classification is empirical. Beyond a few driver mutations, pathophysiology is not well understood. Here, a pangenomic characterization of benign adrenocortical tumors is proposed, aiming at unbiased classification and new pathophysiological insights. Benign adrenocortical tumors (n = 146) were analyzed by transcriptome, methylome, miRNome, chromosomal alterations and mutational status, using expression arrays, methylation arrays, miRNA sequencing, SNP arrays, and exome or targeted next-generation sequencing respectively. Pathological and hormonal data were collected for all tumors. Pangenomic analysis identifies four distinct molecular categories: (1) tumors responsible for overt Cushing, gathering distinct tumor types, sharing a common cAMP/PKA pathway activation by distinct mechanisms; (2) adenomas with mild autonomous cortisol excess and non-functioning adenomas, associated with beta-catenin mutations; (3) primary macronodular hyperplasia with ARMC5 mutations, showing an ovarian expression signature; (4) aldosterone-producing adrenocortical adenomas, apart from other benign tumors. Epigenetic alterations and steroidogenesis seem associated, including CpG island hypomethylation in tumors with no or mild cortisol secretion, miRNA patterns defining specific molecular groups, and direct regulation of steroidogenic enzyme expression by methylation. Chromosomal alterations and somatic mutations are subclonal, found in less than 2/3 of cells. New pathophysiological insights, including distinct molecular signatures supporting the difference between mild autonomous cortisol excess and overt Cushing, ARMC5 implication into the adreno-gonadal differentiation faith, and the subclonal nature of driver alterations in benign tumors, will orient future research. This first genomic classification provides a large amount of data as a starting point.

Supplementary Materials

    • Supplemental Table 1: Clinical data
    • Supplemental Table 2: Different types of OMICs performed for each sample
    • Supplemental Table 3: Somatic mutations identified by exome sequencing
    • Supplemental Table 4: Mutations identified in a set of 8 potential drivers of benign tumorigenesis, using a targeted NGS panel.
    • Supplemental Table 5: Molecular statuses of benign adrenocortical tumors.
    • Supplemental Table 6: Differential signatures of transcriptome groups.
    • Supplemental Table 7: Expression profile in adrenal adenomas (C2B and C2D) of genes of the C1A/C1B malignancy signature.
    • Supplemental Table 8: Aberrant expression of genes in single tumors from the C2B transcriptome group and no mutation identified in cAMP/PKA related genes. Aberrant expression was defined as a Z-score>4 in the sample, considering C2B mRNA cluster as a reference.
    • Supplemental Table 9: Differential signatures of miRNome groups.
    • Supplemental Table 10: List of genes with a significant negative correlation with miRNAs expression
    • Supplemental Table 11: List of CpGs differentially methylated
    • Supplemental Table 12: List of genes with a significant negative correlation between methylation and expression
    • Supplemental Table 13: Chromosomal alterations
    • Supplemental Figure 1: Venn diagram showing the different omics performed on the cohort
    • Supplemental Figure 2: Main driver mutations in benign adrenocortical tumors
    • Supplemental Figure 3: Mutational signatures for ACA and PMAH patients explored with exome sequencing

 

Society for Endocrinology

Sept 2018 onwards Past Year Past 30 Days
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  • Afanasyeva EA, Mestdagh P, Kumps C, Vandesompele J, Ehemann V, Theissen J, Fischer M, Zapatka M, Brors B & Savelyeva L et al. 2011 MicroRNA miR-885-5p targets CDK2 and MCM5, activates p53 and inhibits proliferation and survival. Cell Death and Differentiation 18 974984. (https://doi.org/10.1038/cdd.2010.164)

    • Search Google Scholar
    • Export Citation
  • Alexandrov LB, Nik-Zainal S, Wedge DC, Campbell PJ & Stratton MR 2013 Deciphering signatures of mutational processes operative in human cancer. Cell Reports 3 246259. (https://doi.org/10.1016/j.celrep.2012.12.008)

    • Search Google Scholar
    • Export Citation
  • Alexandrov LB, Jones PH, Wedge DC, Sale JE, Campbell PJ, Nik-Zainal S & Stratton MR 2015 Clock-like mutational processes in human somatic cells. Nature Genetics 47 14021407. (https://doi.org/10.1038/ng.3441)

    • Search Google Scholar
    • Export Citation
  • Aristizabal Prada ET, Castellano I, Sušnik E, Yang Y, Meyer LS, Tetti M, Beuschlein F, Reincke M & Williams TA 2018 Comparative genomics and transcriptome profiling in primary aldosteronism. International Journal of Molecular Sciences 19 1124. (https://doi.org/10.3390/ijms19041124)

    • Search Google Scholar
    • Export Citation
  • Arlt W, Biehl M, Taylor AE, Hahner S, Libé R, Hughes BA, Schneider P, Smith DJ, Stiekema H & Krone N et al. 2011 Urine steroid metabolomics as a biomarker tool for detecting malignancy in adrenal tumors. Journal of Clinical Endocrinology and Metabolism 96 37753784. (https://doi.org/10.1210/jc.2011-1565)

    • Search Google Scholar
    • Export Citation
  • Assié G, Libé R, Espiard S, Rizk-Rabin M, Guimier A, Luscap W, Barreau O, Lefèvre L, Sibony M & Guignat L et al. 2013 ARMC5 mutations in macronodular adrenal hyperplasia with Cushing’s syndrome. New England Journal of Medicine 369 21052114. (https://doi.org/10.1056/NEJMoa1304603)

    • Search Google Scholar
    • Export Citation
  • Assié G, Letouzé E, Fassnacht M, Jouinot A, Luscap W, Barreau O, Omeiri H, Rodriguez S, Perlemoine K & René-Corail F et al. 2014 Integrated genomic characterization of adrenocortical carcinoma. Nature Genetics 46 607612. (https://doi.org/10.1038/ng.2953)

    • Search Google Scholar
    • Export Citation
  • Barreau O, de Reynies A, Wilmot-Roussel H, Guillaud-Bataille M, Auzan C, René-Corail F, Tissier F, Dousset B, Bertagna X & Bertherat J et al. 2012 Clinical and pathophysiological implications of chromosomal alterations in adrenocortical tumors: an integrated genomic approach. Journal of Clinical Endocrinology and Metabolism 97 E301E311. (https://doi.org/10.1210/jc.2011-1588)

    • Search Google Scholar
    • Export Citation
  • Barreau O, Assié G, Wilmot-Roussel H, Ragazzon B, Baudry C, Perlemoine K, René-Corail F, Bertagna X, Dousset B & Hamzaoui N et al. 2013 Identification of a CpG island methylator phenotype in adrenocortical carcinomas. Journal of Clinical Endocrinology and Metabolism 98 E174E184. (https://doi.org/10.1210/jc.2012-2993)

    • Search Google Scholar
    • Export Citation
  • Batista F, Vaiman D, Dausset J, Fellous M & Veitia RA 2007 Potential targets of FOXL2, a transcription factor involved in craniofacial and follicular development, identified by transcriptomics. PNAS 104 33303335. (https://doi.org/10.1073/pnas.0611326104)

    • Search Google Scholar
    • Export Citation
  • Bertherat J, Groussin L, Sandrini F, Matyakhina L, Bei T, Stergiopoulos S, Papageorgiou T, Bourdeau I, Kirschner LS & Vincent-Dejean C et al. 2003 Molecular and functional analysis of PRKAR1A and its locus (17q22–24) in sporadic adrenocortical tumors: 17q losses, somatic mutations, and protein kinase A expression and activity. Cancer Research 63 53085319.

    • Search Google Scholar
    • Export Citation
  • Berthon A, Faucz FR, Espiard S, Drougat L, Bertherat J & Stratakis CA 2017 Age-dependent effects of Armc5 haploinsufficiency on adrenocortical function. Human Molecular Genetics 26 34953507. (https://doi.org/10.1093/hmg/ddx235)

    • Search Google Scholar
    • Export Citation
  • Beuschlein F, Reincke M, Karl M, Travis WD, Jaursch-Hancke C, Abdelhamid S, Chrousos GP & Allolio B 1994 Clonal composition of human adrenocortical neoplasms. Cancer Research 54 49274932.

    • Search Google Scholar
    • Export Citation
  • Bonnet S, Gaujoux S, Launay P, Baudry C, Chokri I, Ragazzon B, Libé R, René-Corail F, Audebourg A & Vacher-Lavenu MC et al. 2011 Wnt/β-catenin pathway activation in adrenocortical adenomas is frequently due to somatic CTNNB1-activating mutations, which are associated with larger and nonsecreting tumors: a study in cortisol-secreting and -nonsecreting tumors. Journal of Clinical Endocrinology and Metabolism 96 E419E426. (https://doi.org/10.1210/jc.2010-1885)

    • Search Google Scholar
    • Export Citation
  • Choi SE, Fu T, Seok S, Kim DH, Yu E, Lee KW, Kang Y, Li X, Kemper B & Kemper JK 2013 Elevated microRNA-34a in obesity reduces NAD+ levels and SIRT1 activity by directly targeting NAMPT. Aging Cell 12 10621072. (https://doi.org/10.1111/acel.12135)

    • Search Google Scholar
    • Export Citation
  • Chou CH, Chang NW, Shrestha S, Hsu SD, Lin YL, Lee WH, Yang CD, Hong HC, Wei TY & Tu SJ et al. 2016 miRTarBase 2016: updates to the experimentally validated miRNA-target interactions database. Nucleic Acids Research 44 D239D247. (https://doi.org/10.1093/nar/gkv1258)

    • Search Google Scholar
    • Export Citation
  • de Joussineau C, Sahut-Barnola I, Levy I, Saloustros E, Val P, Stratakis CA & Martinez A 2012 The cAMP pathway and the control of adrenocortical development and growth. Molecular and Cellular Endocrinology 351 2836. (https://doi.org/10.1016/j.mce.2011.10.006)

    • Search Google Scholar
    • Export Citation
  • de Reyniès A, Assié G, Rickman DS, Tissier F, Groussin L, René-Corail F, Dousset B, Bertagna X, Clauser E & Bertherat J 2009 Gene expression profiling reveals a new classification of adrenocortical tumors and identifies molecular predictors of malignancy and survival. Journal of Clinical Oncology 27 11081115. (https://doi.org/10.1200/JCO.2008.18.5678)

    • Search Google Scholar
    • Export Citation
  • Di Dalmazi G, Fanelli F, Mezzullo M, Casadio E, Rinaldi E, Garelli S, Giampalma E, Mosconi C, Golfieri R & Vicennati V et al. 2015 Steroid profiling by LC-MS/MS in nonsecreting and subclinical cortisol-secreting adrenocortical adenomas. Journal of Clinical Endocrinology and Metabolism 100 35293538. (https://doi.org/10.1210/JC.2015-1992)

    • Search Google Scholar
    • Export Citation
  • Di Dalmazi G, Altieri B, Scholz C, Sbiera S, Luconi M, Waldman J, Kastelan D, Ceccato F, Chiodini I & Arnaldi G et al. 2020 RNA-sequencing and somatic mutation status of adrenocortical tumors: novel pathogenetic insights. Journal of Clinical Endocrinology and Metabolism 105 dgaa616. (https://doi.org/10.1210/clinem/dgaa616)

    • Search Google Scholar
    • Export Citation
  • Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, Batut P, Chaisson M & Gingeras TR 2013 STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29 1521. (https://doi.org/10.1093/bioinformatics/bts635)

    • Search Google Scholar
    • Export Citation
  • Doghman M, Karpova T, Rodrigues GA, Arhatte M, De Moura J, Cavalli LR, Virolle V, Barbry P, Zambetti GP & Figueiredo BC et al. 2007 Increased steroidogenic factor-1 dosage triggers adrenocortical cell proliferation and cancer. Molecular Endocrinology 21 29682987. (https://doi.org/10.1210/me.2007-0120)

    • Search Google Scholar
    • Export Citation
  • Dörner J, Martinez Rodriguez V, Ziegler R, Röhrig T, Cochran RS, Götz RM, Levin MD, Pihlajoki M, Heikinheimo M & Wilson DB 2017 GLI1(+) progenitor cells in the adrenal capsule of the adult mouse give rise to heterotopic gonadal-like tissue. Molecular and Cellular Endocrinology 441 164175. (https://doi.org/10.1016/j.mce.2016.08.043)

    • Search Google Scholar
    • Export Citation
  • El Ghorayeb N, Bourdeau I & Lacroix A 2015 Multiple aberrant hormone receptors in Cushing’s syndrome. European Journal of Endocrinology 173 M45M 60. (https://doi.org/10.1530/EJE-15-0200)

    • Search Google Scholar
    • Export Citation
  • Espiard S, Ragazzon B & Bertherat J 2014 Protein kinase A alterations in adrenocortical tumors. Hormone and Metabolic Research 46 869875. (https://doi.org/10.1055/s-0034-1385908)

    • Search Google Scholar
    • Export Citation
  • Faillot S & Assie G 2016 ENDOCRINE TUMOURS: The genomics of adrenocortical tumors. European Journal of Endocrinology 174 R249R265. (https://doi.org/10.1530/EJE-15-1118)

    • Search Google Scholar
    • Export Citation
  • Fassnacht M, Arlt W, Bancos I, Dralle H, Newell-Price J, Sahdev A, Tabarin A, Terzolo M, Tsagarakis S & Dekkers OM 2016 Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice Guideline in collaboration with the European Network for the Study of Adrenal Tumors. European Journal of Endocrinology 175 G1G34. (https://doi.org/10.1530/EJE-16-0467)

    • Search Google Scholar
    • Export Citation
  • Fernandes-Rosa FL, Boulkroun S & Zennaro MC 2017 Somatic and inherited mutations in primary aldosteronism. Journal of Molecular Endocrinology 59 R47R63. (https://doi.org/10.1530/JME-17-0035)

    • Search Google Scholar
    • Export Citation
  • Garinet S, Néou M, de La Villéon B, Faillot S, Sakat J, Da Fonseca JP, Jouinot A, Le Tourneau C, Kamal M & Luscap-Rondof W et al. 2017 Calling chromosome alterations, DNA methylation statuses, and mutations in tumors by simple targeted next-generation sequencing: a solution for transferring integrated pangenomic studies into routine practice? Journal of Molecular Diagnostics 19 776787. (https://doi.org/10.1016/j.jmoldx.2017.06.005)

    • Search Google Scholar
    • Export Citation
  • Gaujoux R & Seoighe C 2010 A flexible R package for nonnegative matrix factorization. BMC Bioinformatics 11 367. (https://doi.org/10.1186/1471-2105-11-367)

    • Search Google Scholar
    • Export Citation
  • Giordano TJ, Kuick R, Else T, Gauger PG, Vinco M, Bauersfeld J, Sanders D, Thomas DG, Doherty G & Hammer G 2009 Molecular classification and prognostication of adrenocortical tumors by transcriptome profiling. Clinical Cancer Research 15 668676. (https://doi.org/10.1158/1078-0432.CCR-08-1067)

    • Search Google Scholar
    • Export Citation
  • Griffiths-Jones S, Grocock RJ, van Dongen S, Bateman A & Enright AJ 2006 miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Research 34 D140D144. (https://doi.org/10.1093/nar/gkj112)

    • Search Google Scholar
    • Export Citation
  • Howard B, Wang Y, Xekouki P, Faucz FR, Jain M, Zhang L, Meltzer PG, Stratakis CA & Kebebew E 2014 Integrated analysis of genome-wide methylation and gene expression shows epigenetic regulation of CYP11B2 in aldosteronomas. Journal of Clinical Endocrinology and Metabolism 99 E536E543. (https://doi.org/10.1210/jc.2013-3495)

    • Search Google Scholar
    • Export Citation
  • Irizarry RA, Gautier L & Cope LM 2003 An R package for analyses of Affymetrix oligonucleotide arrays. In Statistics for Biology and Health, pp. 102119. New York, NY: Springer. (https://doi.org/10.1007/0-387-21679-0_4)

    • Search Google Scholar
    • Export Citation
  • Kaller M, Liffers ST, Oeljeklaus S, Kuhlmann K, Röh S, Hoffmann R, Warscheid B & Hermeking H 2011 Genome-wide characterization of miR-34a induced changes in protein and mRNA expression by a combined pulsed SILAC and microarray analysis. Molecular and Cellular Proteomics 10 M111.010462. (https://doi.org/10.1074/mcp.M111.010462)

    • Search Google Scholar
    • Export Citation
  • Lacroix A, Bolté E, Tremblay J, Dupré J, Poitras P, Fournier H, Garon J, Garrel D, Bayard F & Taillefer R 1992 Gastric inhibitory polypeptide-dependent cortisol hypersecretion – a new cause of Cushing’s syndrome. New England Journal of Medicine 327 974980. (https://doi.org/10.1056/NEJM199210013271402)

    • Search Google Scholar
    • Export Citation
  • Lefebvre H, Prévost G & Louiset E 2013 Autocrine/paracrine regulatory mechanisms in adrenocortical neoplasms responsible for primary adrenal hypercorticism. European Journal of Endocrinology 169 R115R138. (https://doi.org/10.1530/EJE-13-0308)

    • Search Google Scholar
    • Export Citation
  • Li J & Tibshirani R 2013 Finding consistent patterns: a nonparametric approach for identifying differential expression in RNA-Seq data. Statistical Methods in Medical Research 22 519536. (https://doi.org/10.1177/0962280211428386)

    • Search Google Scholar
    • Export Citation
  • McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, Garimella K, Altshuler D, Gabriel S & Daly M et al. 2010 The genome analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Research 20 12971303. (https://doi.org/10.1101/gr.107524.110)

    • Search Google Scholar
    • Export Citation
  • Meimaridou E, Kowalczyk J, Guasti L, Hughes CR, Wagner F, Frommolt P, Nürnberg P, Mann NP, Banerjee R & Saka HN et al. 2012 Mutations in NNT encoding nicotinamide nucleotide transhydrogenase cause familial glucocorticoid deficiency. Nature Genetics 44 740742. (https://doi.org/10.1038/ng.2299)

    • Search Google Scholar
    • Export Citation
  • Newell-Price J, Bertagna X, Grossman AB & Nieman LK 2006 Cushing’s syndrome. Lancet 367 16051617. (https://doi.org/10.1016/S0140-6736(0668699-6)

    • Search Google Scholar
    • Export Citation
  • Panda H, Chuang TD, Luo X & Chegini N 2012 Endometrial miR-181a and miR-98 expression is altered during transition from normal into cancerous state and target PGR, PGRMC1, CYP19A1, DDX3X, and TIMP3. Journal of Clinical Endocrinology and Metabolism 97 E1316E 1326. (https://doi.org/10.1210/jc.2012-1018)

    • Search Google Scholar
    • Export Citation
  • Popova T, Manié E, Stoppa-Lyonnet D, Rigaill G, Barillot E & Stern MH 2009 Genome alteration print (GAP): a tool to visualize and mine complex cancer genomic profiles obtained by SNP arrays. Genome Biology 10 R128. (https://doi.org/10.1186/gb-2009-10-11-r128)

    • Search Google Scholar
    • Export Citation
  • Prueitt RL & Zinn AR 2001 A fork in the road to fertility. Nature Genetics 27 132134. (https://doi.org/10.1038/84735)

  • Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W & Smyth GK 2015 Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Research 43 e47e47. (https://doi.org/10.1093/nar/gkv007)

    • Search Google Scholar
    • Export Citation
  • Ronchi CL, Sbiera S, Leich E, Henzel K, Rosenwald A, Allolio B & Fassnacht M 2013 Single nucleotide polymorphism array profiling of adrenocortical tumors – evidence for an adenoma carcinoma sequence? PLoS ONE 8 e73959. (https://doi.org/10.1371/journal.pone.0073959)

    • Search Google Scholar
    • Export Citation
  • Ronchi CL, Di Dalmazi G, Faillot S, Sbiera S, Assié G, Weigand I, Calebiro D, Schwarzmayr T, Appenzeller S & Rubin B et al. 2016 Genetic landscape of sporadic unilateral adrenocortical adenomas without PRKACA p.Leu206Arg mutation. Journal of Clinical Endocrinology and Metabolism 101 35263538. (https://doi.org/10.1210/jc.2016-1586)

    • Search Google Scholar
    • Export Citation
  • Rosenthal R, McGranahan N, Herrero J, Taylor BS & Swanton C 2016 DeconstructSigs: delineating mutational processes in single tumors distinguishes DNA repair deficiencies and patterns of carcinoma evolution. Genome Biology 17 31. (https://doi.org/10.1186/s13059-016-0893-4)

    • Search Google Scholar
    • Export Citation
  • Sahut-Barnola I, de Joussineau C, Val P, Lambert-Langlais S, Damon C, Lefrançois-Martinez AM, Pointud JC, Marceau G, Sapin V & Tissier F et al. 2010 Cushing’s syndrome and fetal features resurgence in adrenal cortex-specific Prkar1a knockout mice. PLoS Genetics 6 e1000980. (https://doi.org/10.1371/journal.pgen.1000980)

    • Search Google Scholar
    • Export Citation
  • Stephan EA, Chung TH, Grant CS, Kim S, Von Hoff DD, Trent JM & Demeure MJ 2008 Adrenocortical carcinoma survival rates correlated to genomic copy number variants. Molecular Cancer Therapeutics 7 425431. (https://doi.org/10.1158/1535-7163.MCT-07-0267)

    • Search Google Scholar
    • Export Citation
  • Tili E, Michaille JJ, Luo Z, Volinia S, Rassenti LZ, Kipps TJ & Croce CM 2012 The down-regulation of miR-125b in chronic lymphocytic leukemias leads to metabolic adaptation of cells to a transformed state. Blood 120 26312638. (https://doi.org/10.1182/blood-2012-03-415737)

    • Search Google Scholar
    • Export Citation
  • Tissier F, Cavard C, Groussin L, Perlemoine K, Fumey G, Hagneré AM, René-Corail F, Jullian E, Gicquel C & Bertagna X et al. 2005 Mutations of β-catenin in adrenocortical tumors: activation of the Wnt signaling pathway is a frequent event in both benign and malignant adrenocortical tumors. Cancer Research 65 76227627. (https://doi.org/10.1158/0008-5472.CAN-05-0593)

    • Search Google Scholar
    • Export Citation
  • Walczak EM, Kuick R, Finco I, Bohin N, Hrycaj SM, Wellik DM & Hammer GD 2014 Wnt signaling inhibits adrenal steroidogenesis by cell-autonomous and non-cell-autonomous mechanisms. Molecular Endocrinology 8 14711486. (https://doi.org/10.1210/me.2014-1060)

    • Search Google Scholar
    • Export Citation
  • Wang K, Li M & Hakonarson H 2010 ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Research 38 e164e164. (https://doi.org/10.1093/nar/gkq603)

    • Search Google Scholar
    • Export Citation
  • Wilkerson MD & Hayes DN 2010 ConsensusClusterPlus: a class discovery tool with confidence assessments and item tracking. Bioinformatics 26 15721573. (https://doi.org/10.1093/bioinformatics/btq170)

    • Search Google Scholar
    • Export Citation
  • Wilmot Roussel H, Vezzosi D, Rizk-Rabin M, Barreau O, Ragazzon B, René-Corail F, de Reynies A, Bertherat J & Assié G 2013 Identification of gene expression profiles associated with cortisol secretion in adrenocortical adenomas. Journal of Clinical Endocrinology and Metabolism 98 E1109E 1121. (https://doi.org/10.1210/jc.2012-4237)

    • Search Google Scholar
    • Export Citation
  • Zhang C, Tong J & Huang G 2013 Nicotinamide phosphoribosyl transferase (Nampt) is a target of microRNA-26b in colorectal cancer cells. PLoS ONE 8 e69963. (https://doi.org/10.1371/journal.pone.0069963)

    • Search Google Scholar
    • Export Citation
  • Zheng S, Cherniack AD, Dewal N, Moffitt RA, Danilova L, Murray BA, Lerario AM, Else T, Knijnenburg TA & Ciriello G et al. 2016 Comprehensive pan-genomic characterization of adrenocortical carcinoma. Cancer Cell 29 723736. (https://doi.org/10.1016/j.ccell.2016.04.002)

    • Search Google Scholar
    • Export Citation