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10. Somatic mosaicism underlies X-linked acrogigantism syndrome in sporadic male subjects.

Author

Daly, Adrian, Yuan, Bo, Fina, Frederic, Caberg, Jean-Hubert, Trivellin, Giampaolo, Rostomyan, Liliya, de Herder, Wouter, Naves, Luciana, Metzger, Daniel, Cuny, Thomas, Rabl, Wolfgang, Shah, Nalini, Jaffrain-Rea, Marie-Lise, Zatelli, Maria, Faucz, Fabio, Castermans, Emilie, Nanni-Metellus, Isabelle, Lodish, Maya, Muhammad, Ammar, Palmeira, Leonor, Potorac, Iulia, Mantovani, Giovanna, Neggers, Sebastian, Klein, Marc, Barlier, Anne, Liu, Pengfei, Ouafik, LHoucine, Bours, Vincent, Lupski, James, Stratakis, Constantine, and Beckers, Albert

Subjects
X-LAG syndrome, gigantism, molecular genetics, mosaicism, pituitary, Adult, Female, Genetic Diseases, X-Linked, Gigantism, Humans, Male, Middle Aged, Mosaicism, Polymerase Chain Reaction, Syndrome, Young Adult
Abstract

Somatic mosaicism has been implicated as a causative mechanism in a number of genetic and genomic disorders. X-linked acrogigantism (XLAG) syndrome is a recently characterized genomic form of pediatric gigantism due to aggressive pituitary tumors that is caused by submicroscopic chromosome Xq26.3 duplications that include GPR101 We studied XLAG syndrome patients (n= 18) to determine if somatic mosaicism contributed to the genomic pathophysiology. Eighteen subjects with XLAG syndrome caused by Xq26.3 duplications were identified using high-definition array comparative genomic hybridization (HD-aCGH). We noted that males with XLAG had a decreased log2ratio (LR) compared with expected values, suggesting potential mosaicism, whereas females showed no such decrease. Compared with familial male XLAG cases, sporadic males had more marked evidence for mosaicism, with levels of Xq26.3 duplication between 16.1 and 53.8%. These characteristics were replicated using a novel, personalized breakpoint junction-specific quantification droplet digital polymerase chain reaction (ddPCR) technique. Using a separate ddPCR technique, we studied the feasibility of identifying XLAG syndrome cases in a distinct patient population of 64 unrelated subjects with acromegaly/gigantism, and identified one female gigantism patient who had had increased copy number variation (CNV) threshold for GPR101 that was subsequently diagnosed as having XLAG syndrome on HD-aCGH. Employing a combination of HD-aCGH and novel ddPCR approaches, we have demonstrated, for the first time, that XLAG syndrome can be caused by variable degrees of somatic mosaicism for duplications at chromosome Xq26.3. Somatic mosaicism was shown to occur in sporadic males but not in females with XLAG syndrome, although the clinical characteristics of the disease were similarly severe in both sexes.

Published
2016

12. Natural history, treatment, and long-term follow up of patients with multiple endocrine neoplasia type 2B: an international, multicentre, retrospective study

Author

Castinetti, Frederic, Waguespack, Steven G, Machens, Andreas, Uchino, Shinya, Hasse-Lazar, Kornelia, Sanso, Gabriella, Else, Tobias, Dvorakova, Sarka, Qi, Xiao Ping, Elisei, Rossella, Maia, Ana Luisa, Glod, John, Lourenço, Delmar Muniz, Jr, Valdes, Nuria, Mathiesen, Jes, Wohllk, Nelson, Bandgar, Tushar R, Drui, Delphine, Korbonits, Marta, Druce, Maralyn R, Brain, Caroline, Kurzawinski, Tom, Patocs, Atila, Bugalho, Maria Joao, Lacroix, Andre, Caron, Philippe, Fainstein-Day, Patricia, Borson Chazot, Francoise, Klein, Marc, Links, Thera P, Letizia, Claudio, Fugazzola, Laura, Chabre, Olivier, Canu, Letizia, Cohen, Regis, Tabarin, Antoine, Spehar Uroic, Anita, Maiter, Dominique, Laboureau, Sandrine, Mian, Caterina, Peczkowska, Mariola, Sebag, Frederic, Brue, Thierry, Mirebeau-Prunier, Delphine, Leclerc, Laurence, Bausch, Birke, Berdelou, Amandine, Sukurai, Akihiro, Vlcek, Petr, Krajewska, Jolanta, Barontini, Marta, Vaz Ferreira Vargas, Carla, Valerio, Laura, Ceolin, Lucieli, Akshintala, Srivandana, Hoff, Ana, Godballe, Christian, Jarzab, Barbara, Jimenez, Camilo, Eng, Charis, Imai, Tsuneo, Schlumberger, Martin, Grubbs, Elizabeth, Dralle, Henning, Neumann, Hartmut P, and Baudin, Eric

Published
2019
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15. Factors associated with survival in anaplastic thyroid carcinoma: A multi-center study from the ENDOCAN-TUTHYREF network

Author

JANNIN, Arnaud, primary, Giudici, Fabiola, additional, de la Fouchardiere, Christelle, additional, Al Ghuzlan, Abir, additional, Wassermann, Johanna, additional, Chougnet, Cecile N, additional, Drui, Delphine, additional, Godbert, Yann, additional, Illouz, Frédéric, additional, Bardet, Stéphane, additional, Zanetta, Sylvie, additional, Roudaut, Nathalie, additional, Batisse-Lignier, Marie, additional, Groussin, Lionel, additional, klein, marc olivier, additional, Zerdoud, Slimane, additional, Lamartina, Livia, additional, Baudin, Eric, additional, Decaussin-Petrucci, Myriam, additional, Leteurtre, Emmanuelle, additional, Borson-Chazot, Francoise, additional, Do Cao, Christine, additional, Borget, Isabelle, additional, and Hadoux, Julien, additional

Published
2023
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16. A multicenter phase II study of sunitinib in patients with locally advanced or metastatic differentiated, anaplastic or medullary thyroid carcinomas: mature data from the THYSU study

Author

Ravaud, Alain, de la Fouchardière, Christelle, Caron, Philippe, Doussau, Adelaïde, Do Cao, Christine, Asselineau, Julien, Rodien, Patrice, Pouessel, Damien, Nicolli-Sire, Patricia, Klein, Marc, Bournaud-Salinas, Claire, Wemeau, Jean-Louis, Gimbert, Anne, Picat, Marie-Quitterie, Pedenon, Delphine, Digue, Laurence, Daste, Amaury, Catargi, Bogdan, and Delord, Jean-Pierre

Published
2017
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17. Prognostic indicators in pituitary adenoma surgery: a comprehensive analysis of surgical outcomes and complications.

Author

Riley, George, Scheyer, Nicolas, Klein, Marc, Merlot, Isabelle, Guerci, Bruno, Jeanbert, Elodie, and Demarquet, Lea

Subjects
PITUITARY tumors, SURGICAL complications, SURGICAL indications, REOPERATION, ENDOSCOPIC surgery
Abstract

Objective: The primary aim of this study was to identify predictive factors associated with onset of de-novo clinically significant pituitary insufficiencies following endoscopic endonasal surgery (EES) for pituitary adenomas. The secondary objective explored the predictive factors of surgical success Methods: A retrospective analysis was conducted on 211 patients who underwent EES. Logistic regression models were employed for the primary and secondary objectives. Patients were stratified into specific groups based on surgical indications and prolactin levels for nuanced analysis. Results: Significant predictors for de-novo pituitary insufficiencies included male sex (OR 3.3, CI95% 1.3-8.1, p=0.01), immediate postoperative insufficiencies (OR 5.6, CI95% 2.8-11.1, p<0.001), and HYPRONOS criteria (OR 5.7, CI95% 1.6-20.9, p=0.008). For surgical success, preoperative insufficiencies (OR 0.7, CI95% 0.5-0.9, p=0.008), repeat surgeries (OR 0.1, CI95% 0-0.4, p=0.001), and gonadotroph or somatotroph adenomas were significant. Age and adenoma size were not predictive in multivariate analysis. Furthermore, we observed a "dip and recover" effect of prolactin after surgery and lower prolactin levels at follow-up (< 3 ng/ml) are correlated with more anterior pituitary insufficiencies than normoprolactinemic patients (p = 0.004). Conclusion: This study identifies key predictors for outcomes in pituitary surgery. Our research is the first to employ individualized success criteria for EES, challenging existing perceptions about the role of age and adenoma size. These findings open avenues for nuanced, individualized preoperative risk assessment and postoperative management. [ABSTRACT FROM AUTHOR]

Published
2024
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18. Metastatic Potential and Survival of Duodenal and Pancreatic Tumors in Multiple Endocrine Neoplasia Type 1: A GTE and AFCE Cohort Study (Groupe d’étude des Tumeurs Endocrines and Association Francophone de Chirurgie Endocrinienne)

Author

Vinault, Sandrine, Mariet, Anne-Sophie, Le Bras, Maëlle, Mirallié, Eric, Cardot-Bauters, Catherine, Pattou, François, Ruszniewski, Philippe, Sauvanet, Alain, Chanson, Philippe, Baudin, Eric, Elias, Dominique, Menegaux, Fabrice, Gaujoux, Sébastien, Borson-Chazot, Françoise, Lifante, Jean-Christophe, Caron, Philippe, Carrère, Nicolas, Tabarin, Antoine, Laurent, Christophe, Klein, Marc, Brunaud, Laurent, Niccoli, Patricia, Sebag, Frédéric, Cadiot, Guillaume, Kianmanesh, Reza, Luu, Maxime, Binquet, Christine, and Goudet, Pierre

Published
2020
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25. Factors Associated with Survival in Anaplastic Thyroid Carcinoma: A Multicenter Study from the ENDOCAN-TUTHYREF Network.

Author

Jannin, Arnaud, Giudici, Fabiola, de la Fouchardière, Christelle, Al Ghuzlan, Abir, Wassermann, Johanna, Chougnet, Cecile N., Drui, Delphine, Godbert, Yann, Ilouz, Frédéric, Bardet, Stéphane, Zanetta, Sylvie, Roudaut, Nathalie, Batisse Lignier, Marie, Groussin, Lionel, Klein, Marc, Zerdoud, Slimane, Lamartina, Livia, Baudin, Eric, Decaussin-Petrucci, Myriam, and Leteurtre, Emmanuelle

Subjects
ANAPLASTIC thyroid cancer, THYROID cancer, RADIOTHERAPY, PROPORTIONAL hazards models, NEUTROPHIL lymphocyte ratio, COMBINED modality therapy
Abstract

Background: Anaplastic thyroid carcinoma (ATC) is a rare and frequently fatal type of thyroid cancer. The degree of heterogeneity in survival rates for ATC is incompletely studied. This study evaluated the factors associated with overall survival (OS) of patients with ATC using multicenter real-world data from a national tertiary care center network in France. Methods: In this multicenter, retrospective cohort study, all patients with ATC diagnosed between 2010 and 2020 were identified from the national database of the French ENDOCAN-TUTHYREF network. Factors associated with OS were examined in multivariable analyses using Cox proportional hazards models. Results: The study included 360 patients. Of these, 220 (61%) were female and the median age was 72 years (interquartile range: 62–80). The percentages of patients with pure and mixed (synchronously-transformed) ATC (p-ATC and st-ATC) were 62.5% and 26.7%, respectively. The median OS was 6.8 months [confidence interval, CI: 5.5–8.1]: not reached for stage IVa, 11.4 months [8.2–17.8] for IVb, and 4.6 months [3.5–5.7] for IVc. Surgery, radiation therapy to the neck, chemotherapy, and best supportive care were administered to 69 (19.2%), 214 (59.4%), 254 (70.6%), and 66 (18.3%) patients, respectively. In a multivariable analysis, including stage IVb–IVc patients, significantly higher OS was observed in patients with Eastern Cooperative Oncology Group performance-status of 0–1 (hazard ratio [HR], 0.6; [CI, 0.4–0.9], p < 0.02), stage IVb [HR, 0.5; CI, 0.4–0.8, p < 0.001], and multimodal treatment (surgery and chemoradiotherapy) [HR, 0.07; CI, 0.04–0.1, p < 0.001]. Variables associated with significantly worse OS included: p-ATC (vs. st-ATC) [HR, 1.83; CI, 1.33–2.51, p = 0.001] and a neutrophil-to-lymphocyte ratio (NLR) >5.05 [HR, 2.05, CI, 1.39–3.05, p < 0.001]. Conclusions: Factors independently associated with improved OS in ATC included: European Cooperative Oncology Group performance status, disease stage, multimodality treatment, synchronously transformed ATC, and lower NLR. Long-term OS was observed in selected patients with ATC who underwent multimodal treatment. [ABSTRACT FROM AUTHOR]

Published
2023
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28. Trading

Author

Heussinger, Werner H., Klein, Marc, Raum, Wolfgang, Heussinger, Werner H., Klein, Marc, and Raum, Wolfgang

Published
2000
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30. Hedging

Author

Heussinger, Werner H., Klein, Marc, Raum, Wolfgang, Heussinger, Werner H., Klein, Marc, and Raum, Wolfgang

Published
2000
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31. Informationsquellen

Author

Heussinger, Werner H., Klein, Marc, Raum, Wolfgang, Heussinger, Werner H., Klein, Marc, and Raum, Wolfgang

Published
2000
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34. Systematic detection of mosaicism by using digital NGS reveals three new MEN1 mosaicisms

Author

Lagarde, Arnaud, primary, Mougel, Grégory, additional, Coppin, Lucie, additional, Haissaguerre, Magalie, additional, Le Collen, Lauriane, additional, Mohamed, Amira, additional, Klein, Marc, additional, Odou, Marie-Françoise, additional, Tabarin, Antoine, additional, Brixi, Hedia, additional, Cuny, Thomas, additional, Delemer, Brigitte, additional, Barlier, Anne, additional, and Romanet, Pauline, additional

Published
2022
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38. Multiple endocrine neoplasia type 1 caused by mosaic mutation: clinical follow-up and genetic counseling?

Author

Coppin, Lucie, primary, Giraud, Sophie, additional, Pasmant, Eric, additional, Lagarde, Arnaud, additional, North, Marie-Odile, additional, Le-Collen, Lauriane, additional, Aubert, Valérie, additional, Mougel, Grégory, additional, Ladsous, Miriam, additional, Louboutin, Alyzée, additional, Brixi, Hedia, additional, Haissaguerre, Magalie, additional, Scheyer, Nicolas, additional, Klein, Marc, additional, Tabarin, Antoine, additional, Delemer, Brigitte, additional, Barlier, Anne, additional, Odou, Marie-Françoise, additional, and Romanet, Pauline, additional

Published
2022
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39. Systematic detection of mosaicism by using digital NGS in a cohort of 119 unresolved MEN1 cases reveals 3 new MEN1 mosaicisms

Author

Lagarde, Arnaud, primary, Mougel, Gregory, additional, Coppin, Lucie, additional, Haissaguerre, Magalie, additional, Le, Collen Lauriane, additional, Klein, Marc, additional, Odou, Marie-Francoise, additional, Tabarin, Antoine, additional, Brixi, Hedia, additional, Delemer, Brigitte, additional, Barlier, Anne, additional, and Romanet, Pauline, additional

Published
2022
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42. Thyroidectomy without Radioiodine in Patients with Low-Risk Thyroid Cancer

Author

Leboulleux, Sophie, primary, Bournaud, Claire, additional, Chougnet, Cecile N., additional, Zerdoud, Slimane, additional, Al Ghuzlan, Abir, additional, Catargi, Bogdan, additional, Do Cao, Christine, additional, Kelly, Antony, additional, Barge, Marie-Luce, additional, Lacroix, Ludovic, additional, Dygai, Inna, additional, Vera, Pierre, additional, Rusu, Daniela, additional, Schneegans, Olivier, additional, Benisvy, Danielle, additional, Klein, Marc, additional, Roux, Julie, additional, Eberle, Marie-Claude, additional, Bastie, Delphine, additional, Nascimento, Camila, additional, Giraudet, Anne-Laure, additional, Le Moullec, Nathalie, additional, Bardet, Stéphane, additional, Drui, Delphine, additional, Roudaut, Nathalie, additional, Godbert, Yann, additional, Morel, Olivier, additional, Drutel, Anne, additional, Lamartina, Livia, additional, Schvartz, Claire, additional, Velayoudom, Fritz-Line, additional, Schlumberger, Martin-Jean, additional, Leenhardt, Laurence, additional, and Borget, Isabelle, additional

Published
2022
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