Network


Latest external collaboration on country level. Dive into details by clicking on the dots.

Hotspot


Dive into the research topics where Arnaud Murat is active.

Publication


Featured researches published by Arnaud Murat.


Journal of Clinical Oncology | 2005

Genetic Testing in Pheochromocytoma or Functional Paraganglioma

Laurence Amar; Jérôme Bertherat; Eric Baudin; Christiane Ajzenberg; Brigitte Bressac-de Paillerets; Olivier Chabre; Bernard Chamontin; B. Delemer; Sophie Giraud; Arnaud Murat; Patricia Niccoli-Sire; Stéphane Richard; V. Rohmer; Jean-Louis Sadoul; Laurence Strompf; Martin Schlumberger; Xavier Bertagna; Pierre-François Plouin; Xavier Jeunemaitre; Anne-Paule Gimenez-Roqueplo

PURPOSE To assess the yield and the clinical value of systematic screening of susceptibility genes for patients with pheochromocytoma (pheo) or functional paraganglioma (pgl). PATIENTS AND METHODS We studied 314 patients with a pheo or a functional pgl, including 56 patients having a family history and/or a syndromic presentation and 258 patients having an apparently sporadic presentation. Clinical data and blood samples were collected, and all five major pheo-pgl susceptibility genes (RET, VHL, SDHB, SDHD, and SDHC) were screened. Neurofibromatosis type 1 was diagnosed from phenotypic criteria. RESULTS We have identified 86 patients (27.4%) with a hereditary tumor. Among the 56 patients with a family/syndromic presentation, 13 have had neurofibromatosis type 1, and germline mutations on the VHL, RET, SDHD, and SDHB genes were present in 16, 15, nine, and three patients, respectively. Among the 258 patients with an apparently sporadic presentation, 30 (11.6%) had a germline mutation (18 patients on SDHB, nine patients on VHL, two patients on SDHD, and one patient on RET). Mutation carriers were younger and more frequently had bilateral or extra-adrenal tumors. In patients with an SDHB mutation, the tumors were larger, more frequently extra-adrenal, and malignant. CONCLUSION Genetic testing oriented by family/sporadic presentation should be proposed to all patients with pheo or functional pgl. We suggest an algorithm that would allow the confirmation of suspected inherited disease as well as the diagnosis of unexpected inherited disease.


The Journal of Clinical Endocrinology and Metabolism | 2009

The succinate dehydrogenase genetic testing in a large prospective series of patients with paragangliomas.

Nelly Burnichon; V. Rohmer; Laurence Amar; P. Herman; Sophie Leboulleux; Vincent Darrouzet; Patricia Niccoli; Dominique Gaillard; Gérard Chabrier; Frédéric Chabolle; Isabelle Coupier; P. Thieblot; Pierre Lecomte; J. Bertherat; Nelly Wion-Barbot; Arnaud Murat; Annabelle Venisse; Pierre-François Plouin; Xavier Jeunemaitre; Anne-Paule Gimenez-Roqueplo

CONTEXT Germline mutations in SDHx genes cause hereditary paraganglioma. OBJECTIVE The aim of the study was to assess the indications for succinate dehydrogenase (SDH) genetic testing in a prospective study. DESIGN A total of 445 patients with head and neck and/or thoracic-abdominal or pelvic paragangliomas were recruited over 5 yr in 20 referral centers. In addition to classical direct sequencing of the SDHB, SDHC, and SDHD genes, two methods for detecting large genomic deletions or duplications were used, quantitative multiplex PCR of short fluorescent fragments (QMPSF) and multiplex ligation-dependent probe amplification (MLPA). RESULTS A large variety of SDH germline mutations were found by direct sequencing in 220 patients and by QMPSF and MLPA in 22 patients (9.1%): 130 in SDHD, 96 in SDHB, and 16 in SDHC. Mutation carriers were younger and more frequently had multiple or malignant paraganglioma than patients without mutations. A head and neck paraganglioma was present in 97.7% of the SDHD and 87.5% of the SDHC mutation carriers, but in only 42.7% of the SDHB carriers. A thoracic-abdominal or pelvic location was present in 63.5% of the SDHB, 16.1% of the SDHD, and in 12.5% of the SDHC mutation carriers. Multiple paragangliomas were diagnosed in 66.9% of the SDHD mutation carriers. A malignant paraganglioma was documented in 37.5% of the SDHB, 3.1% of the SDHD, and none of the SDHC mutation carriers. CONCLUSIONS SDH genetic testing, including tests for large genomic deletions, is indicated in all patients with head and neck and/or thoracic-abdominal or pelvic paraganglioma and can be targeted according to clinical criteria.


The Journal of Clinical Endocrinology and Metabolism | 2010

Clinical characteristics and therapeutic responses in patients with Germ-line AIP mutations and pituitary adenomas : An international collaborative study

Adrian Daly; Maria A. Tichomirowa; Patrick Petrossians; Elina Heliövaara; Marie Lise Jaffrain-Rea; Anne Barlier; Luciana A. Naves; Tapani Ebeling; Auli Karhu; Antti Raappana; Laure Cazabat; Ernesto De Menis; Carmen Fajardo Montañana; Gérald Raverot; Robert J. Weil; Timo Sane; Dominique Maiter; Sebastian Neggers; Maria Yaneva; Antoine Tabarin; Elisa Verrua; Eija Eloranta; Arnaud Murat; Outi Vierimaa; Pasi I. Salmela; Philippe Emy; Rodrigo A. Toledo; María Isabel Sabaté; Chiara Villa; Marc Popelier

CONTEXT AIP mutations (AIPmut) give rise to a pituitary adenoma predisposition that occurs in familial isolated pituitary adenomas and less often in sporadic cases. The clinical and therapeutic features of AIPmut-associated pituitary adenomas have not been studied comprehensively. OBJECTIVE The objective of the study was to assess clinical/therapeutic characteristics of AIPmut pituitary adenomas. DESIGN This study was an international, multicenter, retrospective case collection/database analysis. SETTING The study was conducted at 36 tertiary referral endocrine and clinical genetics departments. PATIENTS Patients included 96 patients with germline AIPmut and pituitary adenomas and 232 matched AIPmut-negative acromegaly controls. RESULTS The AIPmut population was predominantly young and male (63.5%); first symptoms occurred as children/adolescents in 50%. At diagnosis, most tumors were macroadenomas (93.3%); extension and invasion was common. Somatotropinomas comprised 78.1% of the cohort; there were also prolactinomas (n = 13), nonsecreting adenomas (n = 7), and a TSH-secreting adenoma. AIPmut somatotropinomas were larger (P = 0.00026), with higher GH levels (P = 0.00068), more frequent extension (P = 0.018) and prolactin cosecretion (P = 0.00023), and occurred 2 decades before controls (P < 0.000001). Gigantism was more common in the AIPmut group (P < 0.000001). AIPmut somatotropinoma patients underwent more surgical interventions (P = 0.00069) and had lower decreases in GH (P = 0.00037) and IGF-I (P = 0.028) and less tumor shrinkage with somatostatin analogs (P < 0.00001) vs. controls. AIPmut prolactinomas occurred generally in young males and frequently required surgery or radiotherapy. CONCLUSIONS AIPmut pituitary adenomas have clinical features that may negatively impact treatment efficacy. Predisposition for aggressive disease in young patients, often in a familial setting, suggests that earlier diagnosis of AIPmut pituitary adenomas may have clinical utility.


American Journal of Human Genetics | 1998

Germ-Line Mutation Analysis in Patients with Multiple Endocrine Neoplasia Type 1 and Related Disorders

Sophie Giraud; Chang X. Zhang; Olga Serova-Sinilnikova; Virginie Wautot; Janine Salandre; Nathalie Buisson; Christine Waterlot; Catherine Bauters; Nicole Porchet; Jean Pierre Aubert; Philippe Emy; Guillaume Cadiot; B. Delemer; Olivier Chabre; Patricia Niccoli; Frédéric Leprat; Françoise Duron; Brigitte Emperauger; Patrick Cougard; Pierre Goudet; Emile Sarfati; Jean Paul Riou; Sylvie Guichard; Michel Rodier; Alain Meyrier; Philippe Caron; Marie Christine Vantyghem; Michel Assayag; Jean Louis Peix; Michel Pugeat

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant syndrome predisposing to tumors of the parathyroid, endocrine pancreas, anterior pituitary, adrenal glands, and diffuse neuroendocrine tissues. The MEN1 gene has been assigned, by linkage analysis and loss of heterozygosity, to chromosome 11q13 and recently has been identified by positional cloning. In this study, a total of 84 families and/or isolated patients with either MEN1 or MEN1-related inherited endocrine tumors were screened for MEN1 germ-line mutations, by heteroduplex and sequence analysis of the MEN1 gene-coding region and untranslated exon 1. Germ-line MEN1 alterations were identified in 47/54 (87%) MEN1 families, in 9/11 (82%) isolated MEN1 patients, and in only 6/19 (31.5%) atypical MEN1-related inherited cases. We characterized 52 distinct mutations in a total of 62 MEN1 germ-line alterations. Thirty-five of the 52 mutations were frameshifts and nonsense mutations predicted to encode for a truncated MEN1 protein. We identified eight missense mutations and five in-frame deletions over the entire coding sequence. Six mutations were observed more than once in familial MEN1. Haplotype analysis in families with identical mutations indicate that these occurrences reflected mainly independent mutational events. No MEN1 germ-line mutations were found in 7/54 (13%) MEN1 families, in 2/11 (18%) isolated MEN1 cases, in 13/19 (68. 5%) MEN1-related cases, and in a kindred with familial isolated hyperparathyroidism. Two hundred twenty gene carriers (167 affected and 53 unaffected) were identified. No evidence of genotype-phenotype correlation was found. Age-related penetrance was estimated to be >95% at age >30 years. Our results add to the diversity of MEN1 germ-line mutations and provide new tools in genetic screening of MEN1 and clinically related cases.


Clinical Cancer Research | 2012

MAX mutations cause hereditary and sporadic pheochromocytoma and paraganglioma.

Nelly Burnichon; Alberto Cascón; Francesca Schiavi; NicolePaes Morales; Iñaki Comino-Méndez; Nasséra Abermil; Lucía Inglada-Pérez; Aguirre A. de Cubas; Laurence Amar; Marta Barontini; Sandra Bernaldo De Quiroś; Jérôome Bertherat; Yves Jean Bignon; Marinus J. Blok; Sara Bobisse; Salud Borrego; Maurizio Castellano; Philippe Chanson; María Dolores Chiara; Eleonora P. M. Corssmit; Mara Giacchè; Ronald R. de Krijger; Tonino Ercolino; Xavier Girerd; Encarna B. Gomez-Garcia; Álvaro Gómez-Graña; Isabelle Guilhem; Frederik J. Hes; Emiliano Honrado; Esther Korpershoek

Purpose: Pheochromocytomas (PCC) and paragangliomas (PGL) are genetically heterogeneous neural crest–derived neoplasms. Recently we identified germline mutations in a new tumor suppressor susceptibility gene, MAX (MYC-associated factor X), which predisposes carriers to PCC. How MAX mutations contribute to PCC/PGL and associated phenotypes remain unclear. This study aimed to examine the prevalence and associated phenotypic features of germline and somatic MAX mutations in PCC/PGL. Design: We sequenced MAX in 1,694 patients with PCC or PGL (without mutations in other major susceptibility genes) from 17 independent referral centers. We screened for large deletions/duplications in 1,535 patients using a multiplex PCR-based method. Somatic mutations were searched for in tumors from an additional 245 patients. The frequency and type of MAX mutation was assessed overall and by clinical characteristics. Results: Sixteen MAX pathogenic mutations were identified in 23 index patients. All had adrenal tumors, including 13 bilateral or multiple PCCs within the same gland (P < 0.001), 15.8% developed additional tumors at thoracoabdominal sites, and 37% had familial antecedents. Age at diagnosis was lower (P = 0.001) in MAX mutation carriers compared with nonmutated cases. Two patients (10.5%) developed metastatic disease. A mutation affecting MAX was found in five tumors, four of them confirmed as somatic (1.65%). MAX tumors were characterized by substantial increases in normetanephrine, associated with normal or minor increases in metanephrine. Conclusions: Germline mutations in MAX are responsible for 1.12% of PCC/PGL in patients without evidence of other known mutations and should be considered in the genetic work-up of these patients. Clin Cancer Res; 18(10); 2828–37. ©2012 AACR.


Annals of Surgery | 2006

Epidemiology data on 108 MEN 1 patients from the GTE with isolated nonfunctioning tumors of the pancreas

Frederic Triponez; David Dosseh; Pierre Goudet; Patrick Cougard; Catherine Bauters; Arnaud Murat; Guillaume Cadiot; Patricia Niccoli-Sire; Jean-Alain Chayvialle; Alain Calender; Charles Proye

Objective:To analyze the penetrance and clinical course of isolated nonfunctioning tumors of the pancreas (NFTP) in MEN 1 patients, and to propose a strategy for managing them. Summary Background Data:Pancreaticoduodenal tumors develop in a majority of MEN 1 patients and are a major cause of death. The natural history of NFTP is poorly defined, and no clear-cut guidelines have been widely accepted regarding treatment. Methods:Data on 108 patients with isolated NFTP among 579 MEN 1 patients from the French Endocrine Tumor Study Group (GTE) were analyzed. Survival rates were calculated using the Kaplan-Meier method. Results:The penetrance of NFTP was 34% at age 50, making it the most frequent pancreaticoduodenal tumor in MEN 1 patients. Forty-three patients (40%) underwent surgery, 32 of them curatively. No patient died because of surgery. Average life expectancy for patients with NFTP was shorter than that for MEN 1 patients who did not have pancreaticoduodenal tumors. Thirteen patients died during follow-up, 10 due to NFTP. Tumor size was correlated with the risks of metastasis and death. These risks were low for patients with tumors ≤20 mm. Conclusions:NFTP are currently the most common tumors of the pancreaticoduodenal region in patients with MEN 1. Prevention of tumor spread by surgery should be balanced with potential operative mortality and morbidity. We do not recommend routine surgery for NFTP ≤20 mm.


American Journal of Human Genetics | 2001

Localization of a susceptibility gene for familial nonmedullary thyroid carcinoma to chromosome 2q21.

James D. McKay; Fabienne Lesueur; Laurence Jonard; Alessandro Pastore; Jan Williamson; L Hoffman; John R. Burgess; Anne Duffield; Mauro Papotti; Markus Stark; Hagay Sobol; Béatrice Maes; Arnaud Murat; Helena Kääriäinen; Mireille Bertholon-Grégoire; Michele Zini; Mary Anne Rossing; Marie-Elisabeth Toubert; Françoise Bonichon; Marie Cavarec; Anne-Marie Bernard; Frédéric Leprat; Oskar A. Haas; Christine Lasset; Martin Schlumberger; Federico Canzian; David E. Goldgar; Giovanni Romeo

The familial form of nonmedullary thyroid carcinoma (NMTC) is a complex genetic disorder characterized by multifocal neoplasia and a higher degree of aggressiveness than its sporadic counterpart. In a large Tasmanian pedigree (Tas1) with recurrence of papillary thyroid carcinoma (PTC), the most common form of NMTC, an extensive genomewide scan revealed a common haplotype on chromosome 2q21 in seven of the eight patients with PTC. To verify the significance of the 2q21 locus, we performed linkage analysis in an independent sample set of 80 pedigrees, yielding a multipoint heterogeneity LOD score (HLOD) of 3.07 (alpha=0.42), nonparametric linkage (NPL) 3.19, (P=.001) at marker D2S2271. Stratification based on the presence of at least one case of the follicular variant of PTC, the phenotype observed in the Tas1 family, identified 17 such pedigrees, yielding a maximal HLOD score of 4.17 (alpha=0.80) and NPL=4.99 (P=.00002) at markers AFMa272zg9 and D2S2271, respectively. These results indicate the existence of a susceptibility locus for familial NMTC on chromosome 2q21.


Gastroenterology | 1999

Prognostic Factors in Patients With Zollinger-Ellison Syndrome and Multiple Endocrine Neoplasia Type 1

Guillaume Cadiot; Albert Vuagnat; Isabelle Doukhan; Arnaud Murat; Guillaume Bonnaud; B. Delemer; Gérard Thiéfin; Albert Beckers; Michel Veyrac; Charles Proye; Philippe Ruszniewski; Michel Mignon

Abstract Background & Aims: Risk factors of metachronous liver metastases and death are not well known in patients with the Zollinger–Ellison syndrome and multiple endocrine neoplasia type 1. These factors were retrospectively determined in 77 patients. Methods: Data chart review was performed. Results: Median follow-up was 102 months (range, 12–366). Surgery was performed on 48 patients, including 9 of the 10 patients with large pancreatic tumors (≥3 cm). Liver metastases developed in 4 patients (40%) with large pancreatic tumors, in 3 (4.8%) without, and in 1 of the 4 patients with pancreatic tumors of unknown size; all had previously undergone surgery. The only independent factor associated with development of liver metastases identified by multivariate analysis was large pancreatic tumors (risk ratio, 29.0; 95% confidence interval [CI], 3.2–260.7). Surgery was not selected. The probability of being free of liver metastases in the 63 patients without large pancreatic tumors was 96% (95% CI, 88–100) at 10 and 15 years. Thirteen (16.9%) patients died. The only independent factors of death selected by multivariate analysis were Zollinger–Ellison syndrome diagnosis before 1980 (risk ratio, 8.2; 95% CI, 1.7–40.6) and age at diagnosis (risk ratio/year, 1.08; 95% CI, 1.03–1.14). Conclusions: Large pancreatic tumors are predictive of the development of metachronous liver metastases, and surgery does not seem to prevent them. GASTROENTEROLOGY 1999;116:286-293


World Journal of Surgery | 2006

Is Surgery Beneficial for MEN1 Patients with Small (≤2 cm), Nonfunctioning Pancreaticoduodenal Endocrine Tumor? An Analysis of 65 Patients from the GTE

Frédéric Triponez; Pierre Goudet; David Dosseh; Patrick Cougard; Catherine Bauters; Arnaud Murat; Guillaume Cadiot; Patricia Niccoli-Sire; Alain Calender; Charles Proye

BackgroundThe management of small, nonfunctioning pancreaticoduodenal endocrine tumors (NFPET) in multiple endocrine neoplasia type 1 (MEN1) patients is still controversial. We therefore investigated the effect of surgery on survival and tumor progression in MEN1 patients with NFPET ≤2 cm by analyzing data from the Groupe des Tumeurs Endocrines (GTE) registry.Materials and MethodsAmong 579 MEN1 patients in the registry, 65 had NFPET ≤ 2 cm. Fifteen (23%) underwent pancreatectomy, 9 at least segmental pancreatectomies and 6 biopsies or enucleations (the surgery group), and 50 (77%) were followed conservatively (the no surgery group). Age at MEN1 and NFPET diagnosis was similar in both groups, as was size of the primary tumor. Seven (10.8%) patients had metastases. Five metastases were synchronous, and 2 (one in each group) were metachronous. Tumor size was similar in patients with or without metastasis.ResultsThere was no perioperative mortality. The average follow-up time after NFPET diagnosis was 6.7 years in the surgery group and 3.3 years in the no surgery group. Three (4.6%) patients died during follow-up, 2 due to NFPET and 1 due to thymus tumor. The 2 patients who died of NFPET had undergone pancreatic surgery at the time of NFPET diagnosis. The 2 groups did not differ significantly with respect to tumor progression [5/15 (33%) vs 6/38 (16%), P = 0.16]. Overall life expectancy of patients with NFPET ≤2 cm was not different than that of the 229 MEN1 patients in the registry without any pancreaticoduodenal tumor (P = 0.33).ConclusionsThis study suggests that surgery may not be beneficial for MEN1 patients with NFPET ≤2 cm.


The American Journal of Gastroenterology | 2006

Prospective endoscopic ultrasonographic evaluation of the frequency of nonfunctioning pancreaticoduodenal endocrine tumors in patients with multiple endocrine neoplasia type 1.

Laurence Thomas-Marques; Arnaud Murat; B. Delemer; A. Penfornis; Catherine Cardot-Bauters; Eric Baudin; Patricia Niccoli-Sire; Damien Levoir; Hélène du Boullay Choplin; Olivier Chabre; Nicolas Jovenin; Guillaume Cadiot

BACKGROUND:The frequency of pancreaticoduodenal endocrine tumors in patients with multiple endocrine neoplasia type 1 (MEN1) remains unknown.AIM:To evaluate prospectively with endoscopic ultrasonography (EUS) the frequency of nonfunctioning (asymptomatic) pancreaticoduodenal tumors.PATIENTS AND METHODS:MEN1 patients without functioning pancreatic involvement underwent systematic pancreaticoduodenal EUS in nine GTE (Groupe des Tumeurs Endocrines) centers. Demographic and clinical factors predictive of pancreatic involvement were sought, and standardized biochemical measurements obtained.RESULTS:Between November 1997 and July 2004, 51 patients (median age: 39 [range: 16–71] yr) were studied. MEN1 had been diagnosed 3 [0–20] yr earlier, notably by genetic screening for 26 (51%) with asymptomatic disease. Twenty-five patients had minor biochemical anomalies (<2 × normal (N)) and serum somatostatin was 10.8 N in 1; EUS detected pancreatic lesions in 28 patients (54.9%; 95% CI: 41.3–68.7%). A median of three [1–9] tumors with a median diameter of 6 [2–60] mm was found per patient; for 19 (37.3%) patients a tumor measured ≥10 mm and ≥ 20 mm in 7 (13.7%) patients. Only one duodenal lesion was found and three patients had peripancreatic adenopathies. Pancreatic tumors were not associated with any of the studied parameters, notably age, family history, biochemical anomalies. Sixteen of twenty-six patients underwent EUS monitoring over 50 [12–70] months; six (37.5%) had more and/or larger pancreatic lesions.CONCLUSION:The frequency of nonfunctioning pancreatic endocrine tumors is higher (54.9%) than previously thought. The size and number of these tumors can increase over time. Pancreatic EUS should be performed once MEN1 is diagnosed to monitor disease progression.

Collaboration


Dive into the Arnaud Murat's collaboration.

Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar

Olivier Chabre

Centre Hospitalier Universitaire de Grenoble

View shared research outputs
Top Co-Authors

Avatar
Top Co-Authors

Avatar

Eric Baudin

Institut Gustave Roussy

View shared research outputs
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Researchain Logo
Decentralizing Knowledge