Identification of Potential Gene Markers and Insights into the Pathophysiology of Pheochromocytoma Malignancy

Erwan Thouennon (1, 2) , Abdel G. Elkahloun (3) , Johann Guillemot (1, 2) , Anne-Paule Gimenez-Roqueplo (4) , Jérôme Bertherat (5) , Alice Pierre (1, 2) , Hafida Ghzili (1, 2) , Luca Grumolato (1, 2) , Mihaela Muresan (6) , Marc Klein (6) , Hervé Lefebvre (1, 2) , L’houcine Ouafik (7) , Hubert Vaudry (1, 2) , Pierre-Francois Plouin (8) , Laurent Yon (1, 2) , Youssef Anouar (1, 2)

1 Neuroendocrinologie cellulaire et moléculaire
2 IFRMP 23 - Institut Fédératif de Recherches Multidisciplinaires sur les Peptides
3 NHGRI - National Human Genome Research Institute
4 HEGP - Hôpital Européen Georges Pompidou [APHP]
5 IC UM3 (UMR 8104 / U1016) - Institut Cochin
6 UMR_S567 / UMR 8104 - Institut Cochin
7 LABORATOIRE DE CANCEROLOGIE INSERM EMI 0359
8 LABORATOIRE DE CANCEROLOGIE EXPERIMENTALE EA2671

Context: Pheochromocytomas are catecholamine-producing tumors that are generally benign but that can also present as or develop into malignancy. Occurrence of malignant pheochromocytomas can only be asserted by imaging of metastatic lesions. Objectives: We conducted a gene expression profiling of benign and malignant tumors to identify a gene signature that would allow us to discriminate benign from malignant pheochromocytomas and to gain a better understanding of tumorigenic pathways associated with malignancy. Design: A total of 36 patients with pheochromocytoma was studied retrospectively. There were 18 (nine benign and nine malignant) tumors used for gene expression profiling on pangenomic oligonucleotide microarrays. Results: We identified and validated a set of predictor genes that could accurately distinguish the two tumor subtypes through unsu-pervised clustering. Most of the differentially expressed genes were down-regulated in malignant tumors, and several of these genes encoded neuroendocrine factors involved in prominent characteristics of chromaffin cell biology. In particular, the expression of two key processing enzymes of trophic peptides, peptidylglycine-amidating monooxygenase and glutaminyl-peptide cyclotransferase, was reduced in malignant pheochromocytomas. Conclusion: The gene expression profiling of benign and malignant pheochromocytomas clearly identified a set of genes that could be used as a prognostic multi-marker and revealed that the expression of several genes encoding neuroendocrine proteins was reduced in malignant compared with benign tumors. (J Clin Endocrinol Metab 92: 4865– 4872, 2007)

Domains: Life Sciences [q-bio]

Erwan Thouennon, Abdel G. Elkahloun, Johann Guillemot, Anne-Paule Gimenez-Roqueplo, Jérôme Bertherat, et al.. Identification of Potential Gene Markers and Insights into the Pathophysiology of Pheochromocytoma Malignancy. Journal of Clinical Endocrinology and Metabolism, 2007, 92 (12), pp.4865 - 4872. ⟨10.1210/jc.2007-1253⟩. ⟨hal-01706427⟩