Anne-Paule GIMENEZ-ROQUEPLO

apgr 2019Anne-Paule GIMENEZ-ROQUEPLO, MD, PhD

Team 13- Genetics and metabolism of rare cancers

After a MD in Endocrinology and a PhD in Genetics, I started research group dedicated to the study of pheochromocytoma and paraganglioma (PPGL) in 2002, which was created as an independent research team “Pheochromocytomas and paragangliomas: from genetics to molecular targeted therapies” in the Paris-Cardiovascular Research Centre in 2014. The team demonstrated that the identification of a SDHB mutation is a risk factor of malignancy and of poor prognosis, identified new PPGL susceptibility genes, revealed the interplay between the tricarboxylic cycle, hypoxic-angiogenesis pathway, epigenomic changes and cancer, established experimental cellular models of SDHx deficient tumors, revealed new therapeutic targets and opened the way to personalized medicine in PPGL. Since 2019, I co-lead with Dr Judith Favier a new version of the team entitled “Genetics and Metabolism of Rare Cancers”.

Current position
  • 2019- : Team Leader, INSERM U970 Team 13- PARCC-HEGP
  • 2008- : Full Professor of Genetics, Faculty of Medicine, Paris Descartes University, Hospital practitioner, Genetics department, Hôpital européen Georges Pompidou, Assistance Publique Hôpitaux de Paris

Education

  • 1995: MD, Paris 5 University
  • 1999: PhD, Paris 6 University
  • 2006: Accreditation to supervise research  (HDR), Paris Descartes University
  • 2016: Aptitude certificate in Hospital Management, Mines ParisTech

Post-graduate training

  • 1989-95: Resident in Medicine, Assistance Publique Hôpitaux de Paris
  • 1995-98: Post-doctoral Fellow, Collège de France, INSERM U36
  • 1998-99: Clinical Fellow in Endocrinology, Broussais Hospital
  • 1999-2002: Clinical Fellow in Genetics, HEGP

Academic positions

  • 2002-2007: Assistant Professor of Genetics, Paris Descartes University & Hôpital Européen Georges      Pompidou, Paris, France
  • 2002-2012: Investigator INSERM (Contrat d’interface INSERM pour hospitaliers) ‘Mitochondrial respiratory chain involvement in the genesis of pheochromocytomas and paragangliomas’
  • 2008-: Professor of Genetics, Paris Descartes University & Hôpital Européen Georges Pompidou, Paris, France
  • 2014-2018: Team leader ‘Pheochromocytomas and paragangliomas: from genetics to molecular  targeted therapies’, INSERM UMR970, Paris research center (PARCC

Participation to scientific committees

  • Chair of the Rare cancers working group (Cancéropôle Ile de France)
  • Past-chair of the Pheochromocytoma and Paraganglioma Research Support Organization (2009-11)
  • Treasurer and member of the executive committee of the European Network for the Study of Adrenal Tumors (ENSAT), past-chair of the Pheochromocytoma and paraganglioma ENSAT working group (2011-17)
  • Member of the healthcare provider center of EURACAN, European reference network for rare cancers
  • Member of the Endocrine Society (ENDO), Expert in Genetics for the ENDO Pheochromocytomas clinical practice guidelines Taskforce (2014)
  • Member of the European Society of Endocrinology, Expert in Genetics for the Pheochromocytomas follow-up guidelines (2015)
  • Member of the European Society of Hypertension; member of the HEGP Hypertension ESH Hypertension Excellence Center; expert in Genetics for The Lancet Commission on Hypertension (2016)
  • Chair of the French registry for SDH-related hereditary paraganglioma (PGL.R)
  • Chair of the COMETE network
  • Coordinator of the Research working group for the French excellence network for rare endocrine diseases (FIRENDO).
  • Member of the Pheochromocytoma/paraganglioma HEGP reference center, component of the National expert center for rare adrenal diseases
  • Member of steering committees of the French excellence network for adrenal cancers (COMETE-Cancer), for rare neuroendocrine tumors (RENATEN) and for familial renal cancers and von Hippel Lindau disease (PREDIR)
  • Member of the steering committee of the French group for endocrine tumors (GTE)
  • Member of different scientific societies in France: the French society of Human Genetics (Treasurer and member of the steering committee from 2011 to 2015); the French society of Endocrinology (member of the steering committee); the French Society of Hypertension; the National Association for molecular genetics practionners (ANPGM, member of the steering committee from 2011 to 2015 ); the French network of oncogenetics laboratories for rare endocrine tumors (TENGEN); the Genetics and Cancer group; the rare tumor committee of the French society of pediatric cancers and leukemias (expert in Genetics)

 

Funding  

  • AAP Fondation ARC 2019 : Pathological role of misoriented cell division in the first phases of kidney cancer (PI: Mario Pende)
  • AO SHS-E-SP 2018 INCA : Prédispositions génétiques aux pathologies malignes de l’enfant et séquençage de nouvelle génération: questions éthiques, légales et psychologiques (PI : S de Montgolfier)
  • Ligue Nationale Contre le Cancer. Labellisation 2017. Equipe “Paragangliomes et phéochromocytomes: de la génétique aux thérapies ciblées” (PI : AP Gimenez-Roqueplo)
  • Cancéropôle Ile de France. EXORARE : mise en place d’une RCP moléculaire de recours pour les cancers rares (PI : AP Gimenez-Roqueplo)
  • AO Foncer contre le cancer 2018 : Evaluation de l’ADN tumoral circulant comme facteur prédictif de réponse au traitement dans le cancer du rein métastatique (PI : N Burnichon)
  • CARPEM : Caractérisation moléculaire de la collection de cancers du rein de l’HEGP (PI : N Burnichon)
  • DGOS/INCA (PRT-K 2014) : COMETE-TACTIC : COMETE network, towards an easy-to use adrenal cancer/tumor identity card (PI : Anne-Paule Gimenez-Roqueplo)
  • INSERM/Institut de Veille Sanitaire R : registre national du paragangliome héréditaire (PI : Anne-Paule Gimenez-Roqueplo)

Teaching activities in international conferences

  • Genetics in pheochromocytoma/paraganglioma. 4th expert meeting “Endocrine hypertension” (9-10 May 2019, Sofia, Bulgaria)
  • Enabling replicative immortality in pheochromocytoma and paraganglioma. 16th International workshop on multiple Endocrine Neoplasia- A focus on new concepts and treatment of malignant manifestations (27-29 March 2019, Houston, USA)
  • VHL in the genomic landscape of pheochromocytomas and paraganglioma. International VHL Medical/Research Symposium, (4-5 October 2018, Houston, USA)
  • Management of pheochromocytoma. ESE Summer school on Endocrinology 2018 (15-18 July, Berlin, Germany)
  • From old syndromes to novel genes: heredity and the value of genetic diagnosis in PPGL. XIII International Symposium GETNE (28-29 September 2017, Cordoba, Spain)
  • From integrative OMICS studies to Precision Medicine in PPGLs. 5th International Symposium on Phaechromocytoma and Paraganglioma (1st September 2017, Sydney, Australia)
  • Clinical implications of SDH mutations. 19th European Congress of Endocrinology (22 May 2017, Lisbon, Portugal)
  • Update in genetic screening. 20th French American Meeting in Endocrinology  (22 March 2017, Bobigny, France)
  • Meet the expert session: Pheochromocytoma. 17th International Congress of Endocrinology (3rd September 2016, Beijing, China)
  • Genetics of pheochromocytoma. 17th International Congress of Endocrinology (1st September 2016, Beijing, China)
  • From multi-omics analysis to precision medicine in paraganglioma and pheochromocytoma. JNI Oncology lecture series. Erasmus MC (22th June 2016, Rotterdam, The Netherlands)
  • The new genetics of phaeochromocytoma. Society for Endocrinology BES 2015 (2nd November 2015, Edinburgh, UK)
  • Familial paragangliomas: genetics and clinical relevance 12th Annual ENETS Conference for the diagnosis and treatment of neuroendocrine tumor disease (13th March 2015, Barcelona, Spain)

Patent

  • 2018: Patent deposit by Inserm Transfert : «Methods for predicting metastatic potential in patients suffering from SDHB-mutated paraganglioma»- EP18306527.5.

 

Publications

189 references PubMed, h index 50, 9 176 citations (July 2019)

 

                  2015-2019

 

  1. Calsina B, Castro-Vega et al. Integrative multi-omics analysis identifies a prognostic miRNA signature and a targetable miR-21-3p/TSC2/mTOR axis in metastatic pheochromocytoma/paraganglioma. 2019
  2. Job S, et al. Telomerase Activation and ATRX Mutations Are Independent Risk Factors for Metastatic Pheochromocytoma and Paraganglioma. Clin Cancer Res. 2019
  3. Ben Aim L, et al. Targeted next-generation sequencing detects rare genetic events in pheochromocytoma and paraganglioma. J Med Genet. 2019
  4. Buffet A, et al Positive impact of genetic test on the management and outcome of patients with paraganglioma and/or pheochromocytoma. J Clin Endocrinol Metab. 2019
  5. Gimenez-Roqueplo AP. Adrenal tumours: when to search for a germline abnormality. Curr Opin Oncol. 2019
  6. Hescot S, et al. Prognosis of malignant pheochromocytoma and paraganglioma (MAPP-Prono study): an ENS@T retrospective study. J Clin Endocrinol Metab. 2019
  7. Buffet A, et al. Germline Mutations in the Mitochondrial 2-Oxoglutarate/Malate Carrier SLC25A11 Gene Confer a Predisposition to Metastatic Paragangliomas. Cancer Res. 2018
  8. Tlemsani C, et al. Chemoresistant pleomorphic rhabdomyosarcoma: whole exome sequencing reveals underlying cancer predisposition and therapeutic options. J Med Genet. 2018
  9. Touat M, et al. Vemurafenib and cobimetinib overcome resistance to vemurafenib in BRAF-mutant ganglioglioma. Neurology. 2018
  10. Pujol P, et al. Guidelines for reporting secondary findings of genome sequencing in cancer genes: the SFMPP recommendations. Eur J Hum Genet. 2018
  11. Calsina B, et al. Role of MDH2 pathogenic variant in pheochromocytoma and paraganglioma patients. Genet Med. 2018
  12. Buffet A, et al. Pheochromocytoma: When to search a germline defect ? Presse Med. 2018
  13. Lenglet M, et al. Identification of a new VHL exon and complex splicing alterations in familial erythrocytosis or von Hippel-Lindau disease. Blood. 2018
  14. Burnichon B, et al. Risk assessment of maternally-inherited SDHD paraganglioma and pheochromocytoma. J Med Genet, 2017
  15. Lebeault M, et al .Nationwide French Study of RET Variants Detected from 2003 to 2013 Suggests a Possible Influence of Polymorphisms as Modifiers. 2017
  16. Lussey-Lepoutre C, et al. Mitochondrial Deficiencies in the Predisposition to Paraganglioma. 2017
  17. Mathiesen JS, et al. Risk Profile of the RET A883F Germline Mutation: An International Collaborative Study. J Clin Endocrinol Metab. 2017
  18. Muller M, et al. Reassessing the clinical spectrum associated with hereditary leiomyomatosis and renal cell carcinoma syndrome in French FH mutation carriers. Clin Genet. 2017
  19. Fishbein L, et al. Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma. Cancer Cell. 2017
  20. Oudijk L, et al. The mTORC1 Complex Is Significantly Overactivated in SDHX-Mutated Paragangliomas. Neuroendocrinology. 2017
  21. Bahougne T, et al. Successful response to pegylated interferon alpha in a patient with recurrent paraganglioma. Endocr Relat Cancer. 2017
  22. Toledo RA, Burnichon N, et al. Consensus Statement on next-generation-sequencing-based diagnostic testing of hereditary phaeochromocytomas and paragangliomas. Nat Rev Endocrinol. 2017
  23. Gravel G, et al. 68Ga-DOTATATE PET/CT Versus MRI: Why the Comparison of 68Ga-DOTATATE PET/CT to an Appropriate MRI Protocol Is Essential. J Nucl Med. 2017
  24. Kiando SR, et al. PHACTR1 Is a Genetic Susceptibility Locus for Fibromuscular Dysplasia Supporting Its Complex Genetic Pattern of Inheritance. PLoS Genet. 2016
  25. Moramarco J, et al Pheochromocytomas are diagnosed incidentally and at older age in neurofibromatosis type 1. Clin Endocrinol (Oxf). 2017
  26. Bourdeau I, et al. A SDHC Founder Mutation Causes Paragangliomas (PGLs) in the French Canadians: New Insights on the SDHC-Related PGL. J Clin Endocrinol Metab. 2016
  27. Olsen MH, et al. A call to action and a lifecourse strategy to address the global burden of raised blood pressure on current and future generations: the Lancet Commission on hypertension. Lancet. 2016
  28. Castro-Vega LJ, et al. The MITF, p.E318K variant as a risk factor for pheochromocytomas and paragangliomas. J Clin Endocrinol Metab. 2016
  29. Plouin PF, et al. European Society of Endocrinology Clinical Practice Guideline for long-term follow-up of patients operated on for a phaeochromocytoma or a paraganglioma. Eur J Endocrinol. 2016
  30. Burnichon N, et al. Pheochromocytoma and paraganglioma: molecular testing and personalized medicine. Curr Opin Oncol. 2016
  31. Lussey-Lepoutre C, et al. Loss of succinate dehydrogenase activity results in dependency on pyruvate carboxylation for cellular anabolism. Commun. 2015
  32. Lussey-Lepoutre C, et al. In vivo detection of succinate by magnetic resonnance spectroscopy as a hallmark of SDHx mutations in paraganglioma. Clin Cancer Res. 2016
  33. Loriot C, et al. Deciphering the molecular basis of invasiveness in Sdhb-deficient cells. 2015
  34. Gravel G, et al. The value of a rapid contrast-enhanced angio-MRI protocol in the detection of head and neck paragangliomas in SDHx mutations carriers: a retrospective study on behalf of the PGL.EVA investigators. Eur Radiol. 2016
  35. Leinhäuser I, et al. Oncogenic features of the bone morphogenic protein 7 (BMP7) in pheochromocytoma. Oncotarget. 2015
  36. Lepoutre-Lussey C, et al. From NF1 to SDHB knockout : the quest for animal models of pheochromocytoma. Mol Cell Endocrinol. 2016
  37. Comino-Méndez I, et al. A Functional and in silico assessment of MAX variants of unknown significance. J Mol Med (Berl). 2015
  38. Castro-Vega LJ, et al. Oncogene. 2016
  39. Oudijk L, et al. Eur J Endocrinol. 2015
  40. Benusiglio PR, et al. A germline mutation in PBRM1 predisposes to renal cell carcinoma. J Med Genet. 2015
  41. de Cubas AA, et al. DNA Methylation Profiling in Pheochromocytoma and Paraganglioma Reveals Diagnostic and Prognostic Markers. Clin Cancer Res. 2015
  42. Oudijk L, et al Vascular pattern analysis for the prediction of clinical behaviour in pheochromocytomas and paragangliomas. PLoS One. 2015
  43. Papathomas TG, et al. SDHB/SDHA immunohistochemistry in pheochromocytomas and paragangliomas: a multicenter interobserver variation analysis using virtual microscopy: a Multinational Study of the European Network for the Study of Adrenal Tumors (ENS@T). Mod Pathol. 2015
  44. Lepoutre-Lussey C, et al. Screening in asymptomatic SDHx mutation carriers: added value of ¹⁸F-FDG PET/CT at initial diagnosis and 1-year follow-up. Eur J Nucl Med Mol Imaging. 2015
  45. Castro-Vega LJ, et al. Multi-omics analysis defines core genomic alterations in pheochromocytomas and paragangliomas. Nat Commun. 2015
  46. Menara M, et al .SDHD immunohistochemistry: a new tool to validate SDHx mutations in pheochromocytoma/paraganglioma. J Clin Endocrinol Metab. 2015
  47. Favier J, et al. Nat Rev Endocrinol. 2015