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Endocrine Abstracts (2017) 49 OC7.2 | DOI: 10.1530/endoabs.49.OC7.2

1Institut Cochin, INSERM U1016, CNRS UMR8104, Paris Descartes University, Paris, France; 2Medical Oncology, Assistance Publique Hôpitaux de Paris, Hôpital Cochin, Paris, France; 3Department of Endocrinology, Assistance Publique Hôpitaux de Paris, Hôpital Cochin, Paris, France; 4Endocrinology and Diabetes Unit, University Hospital, University of Würzburg, Würzburg, Germany; 5Comprehensive Cancer Center Mainfranken, University of Würzburg, Würzburg, Germany; 6Department of Digestive and Endocrine Surgery, Assistance Publique Hôpitaux de Paris, Hôpital Cochin, Paris, France; 7Department of Pathology, Erasmus MC University Medical Center, Rotterdam, The Netherlands; 8Department of Pathology, Reinier de Graaf Hospital, Delft, The Netherlands; 9Department of Surgery, University Hospital Giessen and Marburg, Marburg, Germany; 10Department of Medicine, Charite University, Berlin, Germany; 11Department of Endocrinology, Diabetes and Metabolic Diseases, University Hospital of Bordeaux, Bordeaux, France; 12Department of Endocrinology, University Hospital of Grenoble, Grenoble, France; 13Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy; 14Department of Nuclear Medicine and Endocrine Oncology, Institut Gustave Roussy, Villejuif, France; 15Hypertension Unit, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France; 16Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universität München, München, Germany.


Background: Adrenocortical cancer (ACC) is an aggressive tumour with heterogeneous prognosis. Recently integrated genomics reported distinct genomic alterations: transcriptome “C1A” (high expression of proliferation/cell cycle-related genes) vs “C1B”, “CIMP” (CpG islands hypermethylation) vs “non-CIMP”, chromosome alterations “Noisy” (numerous and anarchic alterations) vs “Chromosomal” (extended patterns of loss of heterozygosity) and “Quiet” (limited alterations), and recurrent somatic mutations in 20 genes. These alterations converge into a single three-groups classification, correlating with outcome. The aim was to develop and validate targeted molecular markers reflecting these genomic groups.

Patients and methods: Two hundred and forty five ACC were included from 21 ENSAT (European network for the Study of Adrenal Tumors) centers. Tumor RNA was assessed by RT-qPCR for BUB1B-PINK1 expression (n=135). Tumor DNA was studied by SNP array for chromosomal alterations (n=238), targeted NGS for mutations of 20 driver genes (n=251), and MS-MLPA for CpG islands methylation of four genes -PAX5, GSTP1, PYCARD, PAX6- (n=221).

Results: Gene expression levels identified “C1A”, “C1B” and “undetermined” ACC in 50, 38 and 12% of cases respectively. Methylation assay identified “CIMP” and “non CIMP” ACC in 44 and 56% of cases respectively. Chromosomal alteration profiles identified “chromosomal”, “noisy” and “quiet” ACC in 55, 32 and 13% of cases respectively. Recurrent mutations or deletions were found in ZNFR3, CDKN2A, TP53 and CTNNB1 in 21, 17, 15 and 11% of cases respectively, in agreement with previous exome studies. All molecular statuses were available for 107 tumors. 87/107 (81%) concordantly recapitulated the 3 main ACC subgroups previously identified by genomic classifications: 37 were “C1A/CIMP”, 18 were “C1A/non-CIMP”, and 32 were “C1B/non-CIMP”. Death events occurred in 34/37, 7/18 and 1/32 patients respectively (Fisher exact P<10–15).

Conclusion: Targeted molecular measures can recapitulate the genomic classification of ACC, giving original and useful prognostication information for patient management.

Volume 49

19th European Congress of Endocrinology

Lisbon, Portugal
20 May 2017 - 23 May 2017

European Society of Endocrinology 

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