ECE2018 Oral Communications Genomic and clinical aspects of endocrine tumours (5 abstracts)
Molecular classification of benign adrenocortical tumors: an integrated genomic study
Simon Faillot 1 , Mario Neou 1 , Stephanie Espiard 1 , Anna Vaczlavik 1 , Simon Garinet 1 , Windy Luscap-Rondof 1 , Anne Jouinot 1 , Ludivine Drougat 1 , Lionel Groussin 1, , Karine Perlemoine 1 , Fernande René-Corail 1 , Bruno Ragazzon 1 , Marthe Rizk-Rabin 1 , Rossella Libe 2 , Frederique Tissier 1, , Aurélien De Reynies 4 , Jerome Bertherat 1, & Guillaume Assié 1,
1Institut Cochin, Inserm U1016, CNRS 8104, Paris Descartes University, Paris, France; 2Department of Endocrinology, Cochin Hospital, Assistance Publique Hôpitaux de Paris, Centre de Référence des Maladies Rares de la Surrénale, Centre de Référence des Cancers Rares de la Surrénale, Paris, France; 3Department of Pathology, Cochin Hospital, Assistance Publique Hôpitaux de Paris, Paris, France; 4La Ligue Contre le Cancer, programme Carte d’Identité des Tumeurs, Paris, France.
Benign adrenal tumors correspond to a spectrum of distinct tumors, including uni- and bilateral diseases with distinct morphological features, and various steroid hormone secretion types and levels. The aim is to study this variability at the molecular level using pan-genomic approaches.
Methods: One hundred and forty six benign adrenal tumors, including adrenocortical adenomas (ACA, N=), primary macronodular adrenal hyperplasia (PMAH, N=), and primary pigmented micronodular dysplasia (PPNAD, N=Cushing’s disease (CD, N=) were included. ACAs secretion was either cortisol (N=), no secretion (N=), mild cortisol secretion (N=), or aldosterone (N=6). Transcriptome, methylome, miRnome and mutational status were generated using Affymetrix U133plus, Illumina Infinium 27k, Illumina sequencing or Life Technologies ampliseq targeted NGS respectively.
Results: Four main molecular groups were identified by transcriptome, methylome, miRnome and mutational status. The largest group gathered cortisol producing tumors, independently of tumor types (ACAs, PMAHs, PPNADs and CDs). These tumors all show cAMP/PKA pathway activation, by distinct mechanisms. Transcriptome identified a steroidogenic signature in this subgroup. The second group gathered the ACAs with no or mild cortisol secretion, and included the majority of beta-catenin mutations. The third group gathered PMAHs with ARMC5 mutations, showing an ovarian expression signature. The last group was exclusively composed of aldosterone-producing ACAs, apart from other benign tumors. Epigenetic alterations and steroidogenesis seemed associated, including CpG island hypomethylation in tumors with no or mild cortisol secretion, miRNA specific patterns in different subgroups, and direct regulation of steroidogenic enzyme expression by methylation.
Conclusion: This first large-scale pangenomic characterization of benign adrenocortical lesions identifies the main molecular subgroups, and represents an important resource to for the study of adrenocortical tumorigenesis and steroidogenesis.
Volume 56
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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