ECE2017 Oral Communications Cardiovascular endocrinology (1) (5 abstracts)
Targeted molecular markers derived from genomic classification for adrenocortical cancer prognostication
Anne Jouinot 1, , Guillaume Assié 1, , Martin Fassnacht 4, , Rossella Libé 1, , Bertrand Dousset 6 , Silviu Sbiera Cristina Ronchi 4 , Matthias Kroiss 5 , Esther Korpershoek 7 , Ronald De Krijger 7, , Jens Waldmann 9 , Marcus Quinkler 10 , Antoine Tabarin 11 , Olivier Chabre 12 , Michaela Luconi 13 , Massimo Mannelli 13 , Lionel Groussin 1, , Eric Baudin 14 , Laurence Amar 15 , Felix Beuschlein 16 & Jérôme Bertherat 1,
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.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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