48 results on '"Janin, Nicolas"'
Search Results
2. Identification of a new VHL exon and complex splicing alterations in familial erythrocytosis or von Hippel-Lindau disease
- Author
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Lenglet, Marion, Robriquet, Florence, Schwarz, Klaus, Camps, Carme, Couturier, Anne, Hoogewijs, David, Buffet, Alexandre, Knight, Samantha J.L., Gad, Sophie, Couvé, Sophie, Chesnel, Franck, Pacault, Mathilde, Lindenbaum, Pierre, Job, Sylvie, Dumont, Solenne, Besnard, Thomas, Cornec, Marine, Dreau, Helene, Pentony, Melissa, Kvikstad, Erika, Deveaux, Sophie, Burnichon, Nelly, Ferlicot, Sophie, Vilaine, Mathias, Mazzella, Jean-Michaël, Airaud, Fabrice, Garrec, Céline, Heidet, Laurence, Irtan, Sabine, Mantadakis, Elpis, Bouchireb, Karim, Debatin, Klaus-Michael, Redon, Richard, Bezieau, Stéphane, Bressac-de Paillerets, Brigitte, Teh, Bin Tean, Girodon, François, Randi, Maria-Luigia, Putti, Maria Caterina, Bours, Vincent, Van Wijk, Richard, Göthert, Joachim R., Kattamis, Antonis, Janin, Nicolas, Bento, Celeste, Taylor, Jenny C., Arlot-Bonnemains, Yannick, Richard, Stéphane, Gimenez-Roqueplo, Anne-Paule, Cario, Holger, and Gardie, Betty
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- 2018
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3. Rapid-onset paraneoplastic cerebellar degeneration successfully treated by radiotherapy and tumorectomy
- Author
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Westerlinck, Philippe, primary, Janin, Nicolas, additional, and Coucke, Philippe, additional
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- 2022
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4. The BRCA1 c. 5096G>A p.Arg1699Gln (R1699Q) intermediate risk variant: breast and ovarian cancer risk estimation and recommendations for clinical management from the ENIGMA consortium
- Author
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Moghadasi, Setareh, Meeks, Huong D, Vreeswijk, Maaike PG, Janssen, Linda AM, Borg, Åke, Ehrencrona, Hans, Paulsson-Karlsson, Ylva, Wappenschmidt, Barbara, Engel, Christoph, Gehrig, Andrea, Arnold, Norbert, Hansen, Thomas Van Overeem, Thomassen, Mads, Jensen, Uffe Birk, Kruse, Torben A, Ejlertsen, Bent, Gerdes, Anne-Marie, Pedersen, Inge Søkilde, Caputo, Sandrine M, Couch, Fergus, Hallberg, Emily J, van den Ouweland, Ans MW, Collée, Margriet J, Teugels, Erik, Adank, Muriel A, van der Luijt, Rob B, Mensenkamp, Arjen R, Oosterwijk, Jan C, Blok, Marinus J, Janin, Nicolas, Claes, Kathleen BM, Tucker, Kathy, Viassolo, Valeria, Toland, Amanda Ewart, Eccles, Diana E, Devilee, Peter, Van Asperen, Christie J, Spurdle, Amanda B, Goldgar, David E, and García, Encarna Gómez
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- 2018
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5. Morphology and genomic hallmarks of breast tumours developed by ATM deleterious variant carriers
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Renault, Anne-Laure, Mebirouk, Noura, Fuhrmann, Laetitia, Bataillon, Guillaume, Cavaciuti, Eve, Le Gal, Dorothée, Girard, Elodie, Popova, Tatiana, La Rosa, Philippe, Beauvallet, Juana, Eon-Marchais, Séverine, Dondon, Marie-Gabrielle, d’Enghien, Catherine Dubois, Laugé, Anthony, Chemlali, Walid, Raynal, Virginie, Labbé, Martine, Bièche, Ivan, Baulande, Sylvain, Bay, Jacques-Olivier, Berthet, Pascaline, Caron, Olivier, Buecher, Bruno, Faivre, Laurence, Fresnay, Marc, Gauthier-Villars, Marion, Gesta, Paul, Janin, Nicolas, Lejeune, Sophie, Maugard, Christine, Moutton, Sébastien, Venat-Bouvet, Laurence, Zattara, Hélène, Fricker, Jean-Pierre, Gladieff, Laurence, Coupier, Isabelle, CoF-AT, GENESIS, kConFab, Chenevix-Trench, Georgia, Hall, Janet, Vincent-Salomon, Anne, Stoppa-Lyonnet, Dominique, Andrieu, Nadine, and Lesueur, Fabienne
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- 2018
- Full Text
- View/download PDF
6. Telomere length, ATM mutation status and cancer risk in Ataxia-Telangiectasia families
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Renault, Anne-Laure, Mebirouk, Noura, Cavaciuti, Eve, Le Gal, Dorothée, Lecarpentier, Julie, d’Enghien, Catherine Dubois, Laugé, Anthony, Dondon, Marie-Gabrielle, Labbé, Martine, Lesca, Gaetan, Leroux, Dominique, Gladieff, Laurence, Adenis, Claude, Faivre, Laurence, Gilbert-Dussardier, Brigitte, Lortholary, Alain, Fricker, Jean-Pierre, Dahan, Karin, Bay, Jacques-Olivier, Longy, Michel, Buecher, Bruno, Janin, Nicolas, Zattara, Hélène, Berthet, Pascaline, Combès, Audrey, Coupier, Isabelle, Hall, Janet, Stoppa-Lyonnet, Dominique, Andrieu, Nadine, and Lesueur, Fabienne
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- 2017
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7. Primary leptomeningeal melanoma is part of the BAP1-related cancer syndrome
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de la Fouchardière, Arnaud, Cabaret, Odile, Pètre, Justine, Aydin, Selda, Leroy, Alice, de Potter, Patrick, Pissaloux, Daniel, Haddad, Véronique, Bressac-de Paillerets, Brigitte, and Janin, Nicolas
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- 2015
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8. BRCA1, BRCA2, TP53, and CDKN2A germline mutations in patients with breast cancer and cutaneous melanoma
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Monnerat, Christian, Chompret, Agnès, Kannengiesser, Caroline, Avril, Marie-Françoise, Janin, Nicolas, Spatz, Alain, Guinebretière, Jean-Marc, Marian, Catalin, Barrois, Michel, Boitier, Françoise, Lenoir, Gilbert M., and Bressac-de Paillerets, Brigitte
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- 2007
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9. A SUMOylation-defective MITF germline mutation predisposes to melanoma and renal carcinoma
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Bertolotto, Corine, Lesueur, Fabienne, Giuliano, Sandy, Strub, Thomas, de Lichy, Mahaut, Bille, Karine, Dessen, Philippe, d’Hayer, Benoit, Mohamdi, Hamida, Remenieras, Audrey, Maubec, Eve, de la Fouchardière, Arnaud, Molinié, Vincent, Vabres, Pierre, Dalle, Stéphane, Poulalhon, Nicolas, Martin-Denavit, Tanguy, Thomas, Luc, Andry-Benzaquen, Pascale, Dupin, Nicolas, Boitier, Françoise, Rossi, Annick, Perrot, Jean-Luc, Labeille, Bruno, Robert, Caroline, Escudier, Bernard, Caron, Olivier, Brugières, Laurence, Saule, Simon, Gardie, Betty, Gad, Sophie, Richard, Stéphane, Couturier, Jérôme, Teh, Bin Tean, Ghiorzo, Paola, Pastorino, Lorenza, Puig, Susana, Badenas, Celia, Olsson, Hakan, Ingvar, Christian, Rouleau, Etienne, Lidereau, Rosette, Bahadoran, Philippe, Vielh, Philippe, Corda, Eve, Blanché, Hélène, Zelenika, Diana, Galan, Pilar, Aubin, François, Bachollet, Bertrand, Becuwe, Céline, Berthet, Pascaline, Jean Bignon, Yves, Bonadona, Valérie, Bonafe, Jean-Louis, Bonnet-Dupeyron, Marie-Noëlle, Cambazard, Fréderic, Chevrant-Breton, Jacqueline, Coupier, Isabelle, Dalac, Sophie, Demange, Liliane, d’Incan, Michel, Dugast, Catherine, Faivre, Laurence, Vincent-Fétita, Lynda, Gauthier-Villars, Marion, Gilbert, Brigitte, Grange, Florent, Grob, Jean-Jacques, Humbert, Philippe, Janin, Nicolas, Joly, Pascal, Kerob, Delphine, Lasset, Christine, Leroux, Dominique, Levang, Julien, Limacher, Jean-Marc, Livideanu, Cristina, Longy, Michel, Lortholary, Alain, Stoppa-Lyonnet, Dominique, Mansard, Sandrine, Mansuy, Ludovic, Marrou, Karine, Matéus, Christine, Maugard, Christine, Meyer, Nicolas, Nogues, Catherine, Souteyrand, Pierre, Venat-Bouvet, Laurence, Zattara, Hélène, Chaudru, Valérie, Lenoir, Gilbert M., Lathrop, Mark, Davidson, Irwin, Avril, Marie-Françoise, Demenais, Florence, Ballotti, Robert, and Bressac-de Paillerets, Brigitte
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- 2011
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10. Novel FH mutations in families with hereditary leiomyomatosis and renal cell cancer (HLRCC) and patients with isolated type 2 papillary renal cell carcinoma
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Gardie, Betty, Remenieras, Audrey, Kattygnarath, Darouna, Bombled, Johny, Lefèvre, Sandrine, Perrier-Trudova, Victoria, Rustin, Pierre, Barrois, Michel, Slama, Abdelhamid, Avril, Marie-Françoise, Bessis, Didier, Caron, Olivier, Caux, Frédéric, Collignon, Patrick, Coupier, Isabelle, Cremin, Carol, Dollfus, Hélène, Dugast, Catherine, Escudier, Bernard, Faivre, Laurence, Field, Michel, Gilbert-Dussardier, Brigitte, Janin, Nicolas, Leport, Yves, Leroux, Dominique, Lipsker, Dan, Malthieu, Félicia, McGilliwray, Barbara, Maugard, Christine, Méjean, Arnaud, Mortemousque, Isabelle, Plessis, Ghislaine, Poppe, Bruce, Pruvost-Balland, Christelle, Rooker, Serena, Roume, Joelle, Soufir, Nadem, Steinraths, Michelle, Tan, Min-Han, Théodore, Christine, Thomas, Luc, Vabres, Pierre, Van Glabeke, Emmanuel, Meric, Jean-Baptiste, Verkarre, Virginie, Lenoir, Gilbert, Joulin, Virginie, Deveaux, Sophie, Cusin, Veronica, Feunteun, Jean, Teh, Bin Tean, Paillerets, Brigitte Bressac-de, and Richard, Stéphane
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- 2011
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11. Cancer Predisposing Missense and Protein Truncating BARD1 Mutations in Non-BRCA1 or BRCA2 Breast Cancer Families
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Brakeleer, Sylvia De, Grève, Jacques De, Loris, Remy, Janin, Nicolas, Lissens, Willy, Sermijn, Erica, and Teugels, Erik
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- 2010
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12. Corrigendum: A SUMOylation-defective MITF germline mutation predisposes to melanoma and renal carcinoma
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Bertolotto, Corine, Lesueur, Fabienne, Giuliano, Sandy, Strub, Thomas, de Lichy, Mahaut, Bille, Karine, Dessen, Philippe, d%apos;Hayer, Benoit, Mohamdi, Hamida, Remenieras, Audrey, Maubec, Eve, de la Fouchardière, Arnaud, Molinié, Vincent, Vabres, Pierre, Dalle, Stéphane, Poulalhon, Nicolas, Martin-Denavit, Tanguy, Thomas, Luc, Andry-Benzaquen, Pascale, Dupin, Nicolas, Boitier, Françoise, Rossi, Annick, Perrot, Jean-Luc, Labeille, Bruno, Robert, Caroline, Escudier, Bernard, Caron, Olivier, Brugières, Laurence, Saule, Simon, Gardie, Betty, Gad, Sophie, Richard, Stéphane, Couturier, Jérôme, Teh, Bin Tean, Ghiorzo, Paola, Pastorino, Lorenza, Puig, Susana, Badenas, Celia, Olsson, Hakan, Ingvar, Christian, Rouleau, Etienne, Lidereau, Rosette, Bahadoran, Philippe, Vielh, Philippe, Corda, Eve, Blanché, Hélène, Zelenika, Diana, Galan, Pilar, Aubin, François, Bachollet, Bertrand, Becuwe, Céline, Berthet, Pascaline, Jean Bignon, Yves, Bonadona, Valérie, Bonafe, Jean-Louis, Bonnet-Dupeyron, Marie-Noëlle, Cambazard, Fréderic, Chevrant-Breton, Jacqueline, Coupier, Isabelle, Dalac, Sophie, Demange, Liliane, d%apos;Incan, Michel, Dugast, Catherine, Faivre, Laurence, Vincent-Fétita, Lynda, Gauthier-Villars, Marion, Gilbert, Brigitte, Grange, Florent, Grob, Jean-Jacques, Humbert, Philippe, Janin, Nicolas, Joly, Pascal, Kerob, Delphine, Lasset, Christine, Leroux, Dominique, Levang, Julien, Limacher, Jean-Marc, Livideanu, Cristina, Longy, Michel, Lortholary, Alain, Stoppa-Lyonnet, Dominique, Mansard, Sandrine, Mansuy, Ludovic, Marrou, Karine, Matéus, Christine, Maugard, Christine, Meyer, Nicolas, Nogues, Catherine, Souteyrand, Pierre, Venat-Bouvet, Laurence, Zattara, Hélène, Chaudru, Valérie, Lenoir, Gilbert M., Lathrop, Mark, Davidson, Irwin, Avril, Marie-Françoise, Demenais, Florence, Ballotti, Robert, and Bressac-de Paillerets, Brigitte
- Subjects
Environmental issues ,Science and technology ,Zoology and wildlife conservation - Abstract
Author(s): Corine Bertolotto; Fabienne Lesueur; Sandy Giuliano; Thomas Strub; Mahaut de Lichy; Karine Bille; Philippe Dessen; Benoit d%apos;Hayer; Hamida Mohamdi; Audrey Remenieras; Eve Maubec; Arnaud de la Fouchardière; Vincent Molinié; [...]
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- 2016
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13. A Simple Model for Carcinogenesis of Colorectal Cancers with Microsatellite Instability
- Author
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Janin, Nicolas, primary
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- 1999
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14. Prenatal diagnosis of acute lymphoblastic leukaemia
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Janin, Nicolas
- Published
- 2000
15. Thec. 5096G>A p.Arg1699Gln (R1699Q) intermediate risk variant : breast and ovarian cancer risk estimation and recommendations for clinical management from the ENIGMA consortium
- Author
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Moghadasi, Setareh, Meeks, Huong D., Vreeswijk, Maaike P G, Janssen, Linda A.M., Borg, Åke, Ehrencrona, Hans, Paulsson-Karlsson, Ylva, Wappenschmidt, Barbara, Engel, Christoph, Gehrig, Andrea, Arnold, Norbert, Van Overeem Hansen, Thomas, Thomassen, Mads, Jensen, Uffe Birk, Kruse, Torben A., Ejlertsen, Bent, Gerdes, Anne Marie, Pedersen, Inge Søkilde, Caputo, Sandrine M., Couch, Fergus J., Hallberg, Emily J., Van Den Ouweland, Ans M W, Collée, J. Margriet, Teugels, Erik, Adank, Muriel A., van der Luijt, Rob B., Mensenkamp, Arjen R., Oosterwijk, Jan C., Blok, Marinus J., Janin, Nicolas, Claes, Kathleen B M, Tucker, Kathy, Viassolo, Valeria, Toland, Amanda Ewart, Eccles, Diana E., Devilee, Peter, Van Asperen, Christie J., Spurdle, Amanda B., Goldgar, David E., and García, Encarna Gómez
- Subjects
Genetics ,Journal Article ,Genetics(clinical) - Abstract
BACKGROUND: We previously showed that theBRCA1variant c.5096G>A p.Arg1699Gln (R1699Q) was associated with an intermediate risk of breast cancer (BC) and ovarian cancer (OC). This study aimed to assess these cancer risks for R1699Q carriers in a larger cohort, including follow-up of previously studied families, to further define cancer risks and to propose adjusted clinical management of femaleBRCA1*R1699Q carriers. METHODS: Data were collected from 129BRCA1*R1699Q families ascertained internationally by ENIGMA (Evidence-based Network for the Interpretation of Germline Mutant Alleles) consortium members. A modified segregation analysis was used to calculate BC and OC risks. Relative risks were calculated under both monogenic model and major gene plus polygenic model assumptions. RESULTS: In this cohort the cumulative risk of BC and OC by age 70 years was 20% and 6%, respectively. The relative risk for developing cancer was higher when using a model that included the effects of both the R1699Q variant and a residual polygenic component compared with monogenic model (for BC 3.67 vs 2.83, and for OC 6.41 vs 5.83). CONCLUSION: Our results confirm thatBRCA1*R1699Q confers an intermediate risk for BC and OC. Breast surveillance for female carriers based on mammogram annually from age 40 is advised. Bilateral salpingo-oophorectomy should be considered based on family history.
- Published
- 2018
16. PCR-assisted localization of the human SRPR gene
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Janin, Nicolas, Delattre, Oliver, and Lipinski, Marc
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- 1992
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17. The BRCA1 c. 5096G > A p.Arg1699Gln (R1699Q) intermediate risk variant : breast and ovarian cancer risk estimation and recommendations for clinical management from the ENIGMA consortium
- Author
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Moghadasi, Setareh, Meeks, Huong D., Vreeswijk, Maaike P. G., Janssen, Linda A. M., Borg, Ake, Ehrencrona, Hans, Paulsson-Karlsson, Ylva, Wappenschmidt, Barbara, Engel, Christoph, Gehrig, Andrea, Arnold, Norbert, Hansen, Thomas Van Overeem, Thomassen, Mads, Jensen, Uffe Birk, Kruse, Torben A., Ejlertsen, Bent, Gerdes, Anne-Marie, Pedersen, Inge Sokilde, Caputo, Sandrine M., Couch, Fergus, Hallberg, Emily J., van den Ouweland, Ans M. W., Collee, Margriet J., Teugels, Erik, Adank, Muriel A., van der Luijt, Rob B., Mensenkamp, Arjen R., Oosterwijk, Jan C., Blok, Marinus J., Janin, Nicolas, Claes, Kathleen B. M., Tucker, Kathy, Viassolo, Valeria, Toland, Amanda Ewart, Eccles, Diana E., Devilee, Peter, Van Asperen, Christie J., Spurdle, Amanda B., Goldgar, David E., Garcia, Encarna Gomez, Moghadasi, Setareh, Meeks, Huong D., Vreeswijk, Maaike P. G., Janssen, Linda A. M., Borg, Ake, Ehrencrona, Hans, Paulsson-Karlsson, Ylva, Wappenschmidt, Barbara, Engel, Christoph, Gehrig, Andrea, Arnold, Norbert, Hansen, Thomas Van Overeem, Thomassen, Mads, Jensen, Uffe Birk, Kruse, Torben A., Ejlertsen, Bent, Gerdes, Anne-Marie, Pedersen, Inge Sokilde, Caputo, Sandrine M., Couch, Fergus, Hallberg, Emily J., van den Ouweland, Ans M. W., Collee, Margriet J., Teugels, Erik, Adank, Muriel A., van der Luijt, Rob B., Mensenkamp, Arjen R., Oosterwijk, Jan C., Blok, Marinus J., Janin, Nicolas, Claes, Kathleen B. M., Tucker, Kathy, Viassolo, Valeria, Toland, Amanda Ewart, Eccles, Diana E., Devilee, Peter, Van Asperen, Christie J., Spurdle, Amanda B., Goldgar, David E., and Garcia, Encarna Gomez
- Abstract
Background: We previously showed that the BRCA1 variant c. 5096G> A p.Arg1699Gln (R1699Q) was associated with an intermediate risk of breast cancer (BC) and ovarian cancer (OC). This study aimed to assess these cancer risks for R1699Q carriers in a larger cohort, including follow-up of previously studied families, to further define cancer risks and to propose adjusted clinical management of female BRCA1* R1699Q carriers. Methods: Data were collected from 129 BRCA1* R1699Q families ascertained internationally by ENIGMA (Evidence-based Network for the Interpretation of Germline Mutant Alleles) consortium members. A modified segregation analysis was used to calculate BC and OC risks. Relative risks were calculated under both monogenic model and major gene plus polygenic model assumptions. Results: In this cohort the cumulative risk of BC and OC by age 70 years was 20% and 6%, respectively. The relative risk for developing cancer was higher when using a model that included the effects of both the R1699Q variant and a residual polygenic component compared with monogenic model (for BC 3.67 vs 2.83, and for OC 6.41 vs 5.83). Conclusion: O ur results confirm that BRCA1* R1699Q confers an intermediate risk for BC and OC. Breast surveillance for female carriers based on mammogram annually from age 40 is advised. Bilateral salpingooophorectomy should be considered based on family history.
- Published
- 2018
- Full Text
- View/download PDF
18. Identification of a new exon and complex splicing alterations in familial erythrocytosis or von Hippel-Lindau disease.
- Author
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UCL - (SLuc) Centre de génétique médicale UCL, Lenglet, Marion, Robriquet, Florence, Schwarz, Klaus, Camps, Carme, Couturier, Anne, Hoogewijs, David, Buffet, Alexandre, Knight, Samantha J L, Gad, Sophie, Couvé, Sophie, Chesnel, Franck, Pacault, Mathilde, Lindenbaum, Pierre, Job, Sylvie, Dumont, Solenne, Besnard, Thomas, Cornec, Marine, Dreau, Helene, Pentony, Melissa, Kvikstad, Erika, Deveaux, Sophie, Burnichon, Nelly, Ferlicot, Sophie, Vilaine, Mathias, Mazzella, Jean-Michaël, Airaud, Fabrice, Garrec, Céline, Heidet, Laurence, Irtan, Sabine, Mantadakis, Elpis, Bouchireb, Karim, Debatin, Klaus-Michael, Redon, Richard, Bezieau, Stéphane, Bressac-de Paillerets, Brigitte, Teh, Bin Tean, Girodon, François, Randi, Maria-Luigia, Putti, Maria Caterina, Bours, Vincent, Van Wijk, Richard, Göthert, Joachim R, Kattamis, Antonis, Janin, Nicolas, Bento, Celeste, Taylor, Jenny C, Arlot-Bonnemains, Yannick, Richard, Stéphane, Gimenez-Roqueplo, Anne-Paule, Cario, Holger, Gardie, Betty, UCL - (SLuc) Centre de génétique médicale UCL, Lenglet, Marion, Robriquet, Florence, Schwarz, Klaus, Camps, Carme, Couturier, Anne, Hoogewijs, David, Buffet, Alexandre, Knight, Samantha J L, Gad, Sophie, Couvé, Sophie, Chesnel, Franck, Pacault, Mathilde, Lindenbaum, Pierre, Job, Sylvie, Dumont, Solenne, Besnard, Thomas, Cornec, Marine, Dreau, Helene, Pentony, Melissa, Kvikstad, Erika, Deveaux, Sophie, Burnichon, Nelly, Ferlicot, Sophie, Vilaine, Mathias, Mazzella, Jean-Michaël, Airaud, Fabrice, Garrec, Céline, Heidet, Laurence, Irtan, Sabine, Mantadakis, Elpis, Bouchireb, Karim, Debatin, Klaus-Michael, Redon, Richard, Bezieau, Stéphane, Bressac-de Paillerets, Brigitte, Teh, Bin Tean, Girodon, François, Randi, Maria-Luigia, Putti, Maria Caterina, Bours, Vincent, Van Wijk, Richard, Göthert, Joachim R, Kattamis, Antonis, Janin, Nicolas, Bento, Celeste, Taylor, Jenny C, Arlot-Bonnemains, Yannick, Richard, Stéphane, Gimenez-Roqueplo, Anne-Paule, Cario, Holger, and Gardie, Betty
- Abstract
Chuvash polycythemia is an autosomal recessive form of erythrocytosis associated with a homozygous p.Arg200Trp mutation in the von Hippel-Lindau () gene. Since this discovery, additional mutations have been identified in patients with congenital erythrocytosis, in a homozygous or compound-heterozygous state. is a major tumor suppressor gene, mutations in which were first described in patients presenting with VHL disease, which is characterized by the development of highly vascularized tumors. Here, we identify a new cryptic exon (termed E1') deep in intron 1 that is naturally expressed in many tissues. More importantly, we identify mutations in E1' in 7 families with erythrocytosis (1 homozygous case and 6 compound-heterozygous cases with a mutation in E1' in addition to a mutation in coding sequences) and in 1 large family with typical VHL disease but without any alteration in the other exons. In this study, we show that the mutations induced a dysregulation of splicing with excessive retention of E1' and were associated with a downregulation of VHL protein expression. In addition, we demonstrate a pathogenic role for synonymous mutations in exon 2 that altered splicing through E2-skipping in 5 families with erythrocytosis or VHL disease. In all the studied cases, the mutations differentially affected splicing, correlating with phenotype severity. This study demonstrates that cryptic exon retention and exon skipping are new alterations and reveals a novel complex splicing regulation of the gene. These findings open new avenues for diagnosis and research regarding the VHL-related hypoxia-signaling pathway.
- Published
- 2018
19. Morphology and genomic hallmarks of breast tumours developed by ATM deleterious variant carriers.
- Author
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UCL - (SLuc) Centre de génétique médicale UCL, Renault, Anne-Laure, Mebirouk, Noura, Fuhrmann, Laetitia, Bataillon, Guillaume, Cavaciuti, Eve, Le Gal, Dorothée, Girard, Elodie, Popova, Tatiana, La Rosa, Philippe, Beauvallet, Juana, Eon-Marchais, Séverine, Dondon, Marie-Gabrielle, d'Enghien, Catherine Dubois, Laugé, Anthony, Chemlali, Walid, Raynal, Virginie, Labbé, Martine, Bièche, Ivan, Baulande, Sylvain, Bay, Jacques-Olivier, Berthet, Pascaline, Caron, Olivier, Buecher, Bruno, Faivre, Laurence, Fresnay, Marc, Gauthier-Villars, Marion, Gesta, Paul, Janin, Nicolas, Lejeune, Sophie, Maugard, Christine, Moutton, Sébastien, Venat-Bouvet, Laurence, Zattara, Hélène, Fricker, Jean-Pierre, Gladieff, Laurence, Coupier, Isabelle, CoF-AT, GENESIS, kConFab, Chenevix-Trench, Georgia, Hall, Janet, Vincent-Salomon, Anne, Stoppa-Lyonnet, Dominique, Andrieu, Nadine, Lesueur, Fabienne, UCL - (SLuc) Centre de génétique médicale UCL, Renault, Anne-Laure, Mebirouk, Noura, Fuhrmann, Laetitia, Bataillon, Guillaume, Cavaciuti, Eve, Le Gal, Dorothée, Girard, Elodie, Popova, Tatiana, La Rosa, Philippe, Beauvallet, Juana, Eon-Marchais, Séverine, Dondon, Marie-Gabrielle, d'Enghien, Catherine Dubois, Laugé, Anthony, Chemlali, Walid, Raynal, Virginie, Labbé, Martine, Bièche, Ivan, Baulande, Sylvain, Bay, Jacques-Olivier, Berthet, Pascaline, Caron, Olivier, Buecher, Bruno, Faivre, Laurence, Fresnay, Marc, Gauthier-Villars, Marion, Gesta, Paul, Janin, Nicolas, Lejeune, Sophie, Maugard, Christine, Moutton, Sébastien, Venat-Bouvet, Laurence, Zattara, Hélène, Fricker, Jean-Pierre, Gladieff, Laurence, Coupier, Isabelle, CoF-AT, GENESIS, kConFab, Chenevix-Trench, Georgia, Hall, Janet, Vincent-Salomon, Anne, Stoppa-Lyonnet, Dominique, Andrieu, Nadine, and Lesueur, Fabienne
- Abstract
BACKGROUND: The ataxia telangiectasia mutated (ATM) gene is a moderate-risk breast cancer susceptibility gene; germline loss-of-function variants are found in up to 3% of hereditary breast and ovarian cancer (HBOC) families who undergo genetic testing. So far, no clear histopathological and molecular features of breast tumours occurring in ATM deleterious variant carriers have been described, but identification of an ATM-associated tumour signature may help in patient management. METHODS: To characterise hallmarks of ATM-associated tumours, we performed systematic pathology review of tumours from 21 participants from ataxia-telangiectasia families and 18 participants from HBOC families, as well as copy number profiling on a subset of 23 tumours. Morphology of ATM-associated tumours was compared with that of 599 patients with no BRCA1 and BRCA2 mutations from a hospital-based series, as well as with data from The Cancer Genome Atlas. Absolute copy number and loss of heterozygosity (LOH) profiles were obtained from the OncoScan SNP array. In addition, we performed whole-genome sequencing on four tumours from ATM loss-of-function variant carriers with available frozen material. RESULTS: We found that ATM-associated tumours belong mostly to the luminal B subtype, are tetraploid and show LOH at the ATM locus at 11q22-23. Unlike tumours in which BRCA1 or BRCA2 is inactivated, tumours arising in ATM deleterious variant carriers are not associated with increased large-scale genomic instability as measured by the large-scale state transitions signature. Losses at 13q14.11-q14.3, 17p13.2-p12, 21p11.2-p11.1 and 22q11.23 were observed. Somatic alterations at these loci may therefore represent biomarkers for ATM testing and harbour driver mutations in potentially 'druggable' genes that would allow patients to be directed towards tailored therapeutic strategies. CONCLUSIONS: Although ATM is involved in the DNA damage response, ATM-associated tumours are distinct from BRCA1-associ
- Published
- 2018
20. The c. 5096G>A p.Arg1699Gln (R1699Q) intermediate risk variant: breast and ovarian cancer risk estimation and recommendations for clinical management from the ENIGMA consortium.
- Author
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UCL - (SLuc) Centre de génétique médicale UCL, Moghadasi, Setareh, Meeks, Huong D, Vreeswijk, Maaike Pg, Janssen, Linda Am, Borg, Åke, Ehrencrona, Hans, Paulsson-Karlsson, Ylva, Wappenschmidt, Barbara, Engel, Christoph, Gehrig, Andrea, Arnold, Norbert, Hansen, Thomas Van Overeem, Thomassen, Mads, Jensen, Uffe Birk, Kruse, Torben A, Ejlertsen, Bent, Gerdes, Anne-Marie, Pedersen, Inge Søkilde, Caputo, Sandrine M, Couch, Fergus, Hallberg, Emily J, van den Ouweland, Ans Mw, Collée, Margriet J, Teugels, Erik, Adank, Muriel A, van der Luijt, Rob B, Mensenkamp, Arjen R, Oosterwijk, Jan C, Blok, Marinus J, Janin, Nicolas, Claes, Kathleen Bm, Tucker, Kathy, Viassolo, Valeria, Toland, Amanda Ewart, Eccles, Diana E, Devilee, Peter, Van Asperen, Christie J, Spurdle, Amanda B, Goldgar, David E, García, Encarna Gómez, UCL - (SLuc) Centre de génétique médicale UCL, Moghadasi, Setareh, Meeks, Huong D, Vreeswijk, Maaike Pg, Janssen, Linda Am, Borg, Åke, Ehrencrona, Hans, Paulsson-Karlsson, Ylva, Wappenschmidt, Barbara, Engel, Christoph, Gehrig, Andrea, Arnold, Norbert, Hansen, Thomas Van Overeem, Thomassen, Mads, Jensen, Uffe Birk, Kruse, Torben A, Ejlertsen, Bent, Gerdes, Anne-Marie, Pedersen, Inge Søkilde, Caputo, Sandrine M, Couch, Fergus, Hallberg, Emily J, van den Ouweland, Ans Mw, Collée, Margriet J, Teugels, Erik, Adank, Muriel A, van der Luijt, Rob B, Mensenkamp, Arjen R, Oosterwijk, Jan C, Blok, Marinus J, Janin, Nicolas, Claes, Kathleen Bm, Tucker, Kathy, Viassolo, Valeria, Toland, Amanda Ewart, Eccles, Diana E, Devilee, Peter, Van Asperen, Christie J, Spurdle, Amanda B, Goldgar, David E, and García, Encarna Gómez
- Abstract
We previously showed that the variant c.5096G>A p.Arg1699Gln (R1699Q) was associated with an intermediate risk of breast cancer (BC) and ovarian cancer (OC). This study aimed to assess these cancer risks for R1699Q carriers in a larger cohort, including follow-up of previously studied families, to further define cancer risks and to propose adjusted clinical management of female *R1699Q carriers. Data were collected from 129 *R1699Q families ascertained internationally by ENIGMA (Evidence-based Network for the Interpretation of Germline Mutant Alleles) consortium members. A modified segregation analysis was used to calculate BC and OC risks. Relative risks were calculated under both monogenic model and major gene plus polygenic model assumptions. In this cohort the cumulative risk of BC and OC by age 70 years was 20% and 6%, respectively. The relative risk for developing cancer was higher when using a model that included the effects of both the R1699Q variant and a residual polygenic component compared with monogenic model (for BC 3.67 vs 2.83, and for OC 6.41 vs 5.83). Our results confirm that *R1699Q confers an intermediate risk for BC and OC. Breast surveillance for female carriers based on mammogram annually from age 40 is advised. Bilateral salpingo-oophorectomy should be considered based on family history.
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- 2018
21. Thec. 5096G>A p.Arg1699Gln (R1699Q) intermediate risk variant: breast and ovarian cancer risk estimation and recommendations for clinical management from the ENIGMA consortium
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Genetica Sectie Genoomdiagnostiek, Cancer, Moghadasi, Setareh, Meeks, Huong D., Vreeswijk, Maaike P G, Janssen, Linda A.M., Borg, Åke, Ehrencrona, Hans, Paulsson-Karlsson, Ylva, Wappenschmidt, Barbara, Engel, Christoph, Gehrig, Andrea, Arnold, Norbert, Van Overeem Hansen, Thomas, Thomassen, Mads, Jensen, Uffe Birk, Kruse, Torben A., Ejlertsen, Bent, Gerdes, Anne Marie, Pedersen, Inge Søkilde, Caputo, Sandrine M., Couch, Fergus J., Hallberg, Emily J., Van Den Ouweland, Ans M W, Collée, J. Margriet, Teugels, Erik, Adank, Muriel A., van der Luijt, Rob B., Mensenkamp, Arjen R., Oosterwijk, Jan C., Blok, Marinus J., Janin, Nicolas, Claes, Kathleen B M, Tucker, Kathy, Viassolo, Valeria, Toland, Amanda Ewart, Eccles, Diana E., Devilee, Peter, Van Asperen, Christie J., Spurdle, Amanda B., Goldgar, David E., García, Encarna Gómez, Genetica Sectie Genoomdiagnostiek, Cancer, Moghadasi, Setareh, Meeks, Huong D., Vreeswijk, Maaike P G, Janssen, Linda A.M., Borg, Åke, Ehrencrona, Hans, Paulsson-Karlsson, Ylva, Wappenschmidt, Barbara, Engel, Christoph, Gehrig, Andrea, Arnold, Norbert, Van Overeem Hansen, Thomas, Thomassen, Mads, Jensen, Uffe Birk, Kruse, Torben A., Ejlertsen, Bent, Gerdes, Anne Marie, Pedersen, Inge Søkilde, Caputo, Sandrine M., Couch, Fergus J., Hallberg, Emily J., Van Den Ouweland, Ans M W, Collée, J. Margriet, Teugels, Erik, Adank, Muriel A., van der Luijt, Rob B., Mensenkamp, Arjen R., Oosterwijk, Jan C., Blok, Marinus J., Janin, Nicolas, Claes, Kathleen B M, Tucker, Kathy, Viassolo, Valeria, Toland, Amanda Ewart, Eccles, Diana E., Devilee, Peter, Van Asperen, Christie J., Spurdle, Amanda B., Goldgar, David E., and García, Encarna Gómez
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- 2018
22. The BRCA1 c. 5096G>A p.Arg1699Gln (R1699Q) intermediate risk variant:breast and ovarian cancer risk estimation and recommendations for clinical management from the ENIGMA consortium
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Moghadasi, Setareh, Meeks, Huong D, Vreeswijk, Maaike Pg, Janssen, Linda Am, Borg, Åke, Ehrencrona, Hans, Paulsson-Karlsson, Ylva, Wappenschmidt, Barbara, Engel, Christoph, Gehrig, Andrea, Arnold, Norbert, Hansen, Thomas Van Overeem, Thomassen, Mads, Jensen, Uffe Birk, Kruse, Torben A, Ejlertsen, Bent, Gerdes, Anne-Marie, Pedersen, Inge Søkilde, Caputo, Sandrine M, Couch, Fergus, Hallberg, Emily J, van den Ouweland, Ans Mw, Collée, Margriet J, Teugels, Erik, Adank, Muriel A, van der Luijt, Rob B, Mensenkamp, Arjen R, Oosterwijk, Jan C, Blok, Marinus J, Janin, Nicolas, Claes, Kathleen Bm, Tucker, Kathy, Viassolo, Valeria, Toland, Amanda Ewart, Eccles, Diana E, Devilee, Peter, Van Asperen, Christie J, Spurdle, Amanda B, Goldgar, David E, García, Encarna Gómez, Moghadasi, Setareh, Meeks, Huong D, Vreeswijk, Maaike Pg, Janssen, Linda Am, Borg, Åke, Ehrencrona, Hans, Paulsson-Karlsson, Ylva, Wappenschmidt, Barbara, Engel, Christoph, Gehrig, Andrea, Arnold, Norbert, Hansen, Thomas Van Overeem, Thomassen, Mads, Jensen, Uffe Birk, Kruse, Torben A, Ejlertsen, Bent, Gerdes, Anne-Marie, Pedersen, Inge Søkilde, Caputo, Sandrine M, Couch, Fergus, Hallberg, Emily J, van den Ouweland, Ans Mw, Collée, Margriet J, Teugels, Erik, Adank, Muriel A, van der Luijt, Rob B, Mensenkamp, Arjen R, Oosterwijk, Jan C, Blok, Marinus J, Janin, Nicolas, Claes, Kathleen Bm, Tucker, Kathy, Viassolo, Valeria, Toland, Amanda Ewart, Eccles, Diana E, Devilee, Peter, Van Asperen, Christie J, Spurdle, Amanda B, Goldgar, David E, and García, Encarna Gómez
- Abstract
BACKGROUND: We previously showed that the BRCA1 variant c.5096G>A p.Arg1699Gln (R1699Q) was associated with an intermediate risk of breast cancer (BC) and ovarian cancer (OC). This study aimed to assess these cancer risks for R1699Q carriers in a larger cohort, including follow-up of previously studied families, to further define cancer risks and to propose adjusted clinical management of female BRCA1*R1699Q carriers.METHODS: Data were collected from 129 BRCA1*R1699Q families ascertained internationally by ENIGMA (Evidence-based Network for the Interpretation of Germline Mutant Alleles) consortium members. A modified segregation analysis was used to calculate BC and OC risks. Relative risks were calculated under both monogenic model and major gene plus polygenic model assumptions.RESULTS: In this cohort the cumulative risk of BC and OC by age 70 years was 20% and 6%, respectively. The relative risk for developing cancer was higher when using a model that included the effects of both the R1699Q variant and a residual polygenic component compared with monogenic model (for BC 3.67 vs 2.83, and for OC 6.41 vs 5.83).CONCLUSION: Our results confirm that BRCA1*R1699Q confers an intermediate risk for BC and OC. Breast surveillance for female carriers based on mammogram annually from age 40 is advised. Bilateral salpingo-oophorectomy should be considered based on family history.
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- 2018
23. Diffuse cortical atrophy in a patient with Turner syndrome and Leber hereditary optic neuropathy
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Blaise, Pierre, Fumal, Arnaud, Janin, Nicolas, Verloes, Alain, Moonen, Gustave, and Andris, Cécile
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- 2005
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24. Telomere length, ATM mutation status and cancer risk in Ataxia-Telangiectasia families.
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UCL - (SLuc) Service de néphrologie, UCL - (SLuc) Centre de génétique médicale UCL, Renault, Anne-Laure, Mebirouk, Noura, Cavaciuti, Eve, Le Gal, Dorothée, Lecarpentier, Julie, d'Enghien, Catherine Dubois, Laugé, Anthony, Dondon, Marie-Gabrielle, Labbé, Martine, Lesca, Gaetan, Leroux, Dominique, Gladieff, Laurence, Adenis, Claude, Faivre, Laurence, Gilbert-Dussardier, Brigitte, Lortholary, Alain, Fricker, Jean-Pierre, Dahan, Karin, Bay, Jacques-Olivier, Longy, Michel, Buecher, Bruno, Janin, Nicolas, Zattara, Hélène, Berthet, Pascaline, Combès, Audrey, Coupier, Isabelle, CoF-AT study collaborators, Hall, Janet, Stoppa-Lyonnet, Dominique, Andrieu, Nadine, Lesueur, Fabienne, UCL - (SLuc) Service de néphrologie, UCL - (SLuc) Centre de génétique médicale UCL, Renault, Anne-Laure, Mebirouk, Noura, Cavaciuti, Eve, Le Gal, Dorothée, Lecarpentier, Julie, d'Enghien, Catherine Dubois, Laugé, Anthony, Dondon, Marie-Gabrielle, Labbé, Martine, Lesca, Gaetan, Leroux, Dominique, Gladieff, Laurence, Adenis, Claude, Faivre, Laurence, Gilbert-Dussardier, Brigitte, Lortholary, Alain, Fricker, Jean-Pierre, Dahan, Karin, Bay, Jacques-Olivier, Longy, Michel, Buecher, Bruno, Janin, Nicolas, Zattara, Hélène, Berthet, Pascaline, Combès, Audrey, Coupier, Isabelle, CoF-AT study collaborators, Hall, Janet, Stoppa-Lyonnet, Dominique, Andrieu, Nadine, and Lesueur, Fabienne
- Abstract
Recent studies have linked constitutive telomere length (TL) to aging-related diseases including cancer at different sites. ATM participates in the signaling of telomere erosion, and inherited mutations in ATM have been associated with increased risk of cancer, particularly breast cancer. The goal of this study was to investigate whether carriage of an ATM mutation and TL interplay to modify cancer risk in ataxia-telangiectasia (A-T) families.The study population consisted of 284 heterozygous ATM mutation carriers (HetAT) and 174 non-carriers (non-HetAT) from 103 A-T families. Forty-eight HetAT and 14 non-HetAT individuals had cancer, among them 25 HetAT and 6 non-HetAT were diagnosed after blood sample collection. We measured mean TL using a quantitative PCR assay and genotyped seven single-nucleotide polymorphisms (SNPs) recurrently associated with TL in large population-based studies.HetAT individuals were at increased risk of cancer (OR = 2.3, 95%CI = 1.2-4.4, P = 0.01), and particularly of breast cancer for women (OR = 2.9, 95%CI = 1.2-7.1, P = 0.02), in comparison to their non-HetAT relatives. HetAT individuals had longer telomeres than non-HetAT individuals (P = 0.0008) but TL was not associated with cancer risk, and no significant interaction was observed between ATM mutation status and TL. Furthermore, rs9257445 (ZNF311) was associated with TL in HetAT subjects and rs6060627 (BCL2L1) modified cancer risk in HetAT and non-HetAT women.Our findings suggest that carriage of an ATM mutation impacts on the age-related TL shortening and that TL per se is not related to cancer risk in ATM carriers. TL measurement alone is not a good marker for predicting cancer risk in A-T families.
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- 2017
25. The BRCA1 c. 5096G>A p.Arg1699Gln (R1699Q) intermediate risk variant: breast and ovarian cancer risk estimation and recommendations for clinical management from the ENIGMA consortium
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Moghadasi, Setareh, primary, Meeks, Huong D, additional, Vreeswijk, Maaike PG, additional, Janssen, Linda AM, additional, Borg, Åke, additional, Ehrencrona, Hans, additional, Paulsson-Karlsson, Ylva, additional, Wappenschmidt, Barbara, additional, Engel, Christoph, additional, Gehrig, Andrea, additional, Arnold, Norbert, additional, Hansen, Thomas Van Overeem, additional, Thomassen, Mads, additional, Jensen, Uffe Birk, additional, Kruse, Torben A, additional, Ejlertsen, Bent, additional, Gerdes, Anne-Marie, additional, Pedersen, Inge Søkilde, additional, Caputo, Sandrine M, additional, Couch, Fergus, additional, Hallberg, Emily J, additional, van den Ouweland, Ans MW, additional, Collée, Margriet J, additional, Teugels, Erik, additional, Adank, Muriel A, additional, van der Luijt, Rob B, additional, Mensenkamp, Arjen R, additional, Oosterwijk, Jan C, additional, Blok, Marinus J, additional, Janin, Nicolas, additional, Claes, Kathleen BM, additional, Tucker, Kathy, additional, Viassolo, Valeria, additional, Toland, Amanda Ewart, additional, Eccles, Diana E, additional, Devilee, Peter, additional, Van Asperen, Christie J, additional, Spurdle, Amanda B, additional, Goldgar, David E, additional, and García, Encarna Gómez, additional
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- 2017
- Full Text
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26. Primary leptomeningeal melanoma is part of the BAP1-related cancer syndrome
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UCL - SSS/IONS/NEUR - Clinical Neuroscience, UCL - (SLuc) Service d'ophtalmologie, de la Fouchardière, Arnaud, Cabaret, Odile, Pètre, Justine, Aydin, Selda, Leroy, Alice, de Potter, Patrick, Pissaloux, Daniel, Haddad, Véronique, Bressac-de Paillerets, Brigitte, Janin, Nicolas, UCL - SSS/IONS/NEUR - Clinical Neuroscience, UCL - (SLuc) Service d'ophtalmologie, de la Fouchardière, Arnaud, Cabaret, Odile, Pètre, Justine, Aydin, Selda, Leroy, Alice, de Potter, Patrick, Pissaloux, Daniel, Haddad, Véronique, Bressac-de Paillerets, Brigitte, and Janin, Nicolas
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- 2015
27. Genotype-phenotype correlations in a series of patients with von Hippel-Lindau disease in one single tertiary centre
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Furnica, Raluca Maria, primary, Janin, Nicolas, additional, and Maiter, Dominique, additional
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- 2015
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28. Familial adhesive arachnoiditis associated with syringomyelia
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UCL - (SLuc) Centre de génétique médicale UCL, Pasoglou, Vasiliki, Janin , Nicolas, Tebache, Malek, Tegos, Thomas J, Born, Jacques D, Collignon, Laurent, UCL - (SLuc) Centre de génétique médicale UCL, Pasoglou, Vasiliki, Janin , Nicolas, Tebache, Malek, Tegos, Thomas J, Born, Jacques D, and Collignon, Laurent
- Abstract
Adhesive arachnoiditis is a rare condition, often complicated by syringomyelia. This pathologic entity is usually associated with prior spinal surgery, spinal inflammation or infection, and hemorrhage. The usual symptoms of arachnoiditis are pain, paresthesia, and weakness of the low extremities due to the nerve entrapment. A few cases have had no obvious etiology. Previous studies have reported one family with multiple cases of adhesive arachnoiditis. We report a second family of Belgian origin with multiple cases of arachnoiditis and secondary syringomyelia in the affected individuals.
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- 2014
29. Etude de cohorte française sur l'ataxie-télangiectasie (CoF-AT) : 2003-2008
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Cavaciuti, Eve, Dubois d'Enghien, Catherine, Laugé, Anthony, Troude, Pénélope, Dondon, Marie-Gabrielle, Labbé, Martine, Janin, Nicolas, Coupier, Isabelle, Bay, Jacques-Olivier, Hall, Janet, Stoppa-Lyonnet, Dominique, Andrieu, Nadine, Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Institut Curie [Paris]-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Génétique Oncologique, Institut Curie [Paris], Département de génétique Humaine, CHU Sart Tilman, Service de Génétique Médicale, Hôpital Arnaud de Villeneuve, Unité d'Oncogénétique, CRLCC Val d'Aurelle - Paul Lamarque, Unité de transplantation médullaire et laboratoire d'oncologie moléculaire, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER-UNICANCER, Génotoxicologie, signalisation et radiothérapie expérimentale, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie [Paris], Groupe Cof-At, Cancer et génôme: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -INSTITUT CURIE, INSTITUT CURIE, CRLCC Jean Perrin, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -INSTITUT CURIE, Dondon, Marie-Gabrielle, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)
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[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,[ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie - Abstract
National audience; Objectifs Les objectifs de l’étude CoF-AT sont d’estimer précisément le risque de cancer associé aux gènes de l’Ataxie Télangiectasie (A-T), de rechercher les facteurs de risque associés, d’étudier les caractéristiques du cancer du sein (CS) chez les hétérozygotes A-T et de proposer une surveillancemammaire aux femmes apparentées à un enfant atteint d’A-T. Contexte En effet, plusieurs études familiales ont montré une augmentation du risque de cancer et en particulier de cancer du sein parmi les apparentés des enfants A-T (ex : Swift 1987, Janin et al., 1999, Olsen et al., 2005, Thompson et al., 2005) et bien que l’A-T soit une maladie génétique rare (entre 1 cas sur 100 000 naissances et 1 sur 40 000), transmise selon le mode récessif, on estime autour de 0.5 % la proportion d’hétérozygotespour les gènes de l’A-T dans la population générale. Ce trait génétique pourrait donc être impliqué dans un pourcentage non négligeable de CS. L’A-T est une maladie de l’enfant caractérisée par une ataxie cérébelleuse dégénérative, des télangiectasies cutanées ou muqueuses, un déficit immunitaireet un risque augmenté de cancer. Deux gènes responsables de la maladie et codant des protéines impliquées dans la réparation des cassures double-brin de l’ADN ont été identifiés : ATM (Savitsky et al., 1995) et MRE11 (Stewart et al., 1999). Protocole : Une cohorte de femmes apparentées à un enfant atteint d’A-T est en cours de constitution depuis mai 2003. Un total de 800 inclusions de femmes hétérozygotes et non-hétérozygotes est attendu. Les femmes appartiennent aux familles recrutées lorsde l’étude familiale rétrospective (Janin et al., 1999) et aux nouvelles familles identifiées dans le cadre du diagnostic des enfants atteints. Ces nouvelles familles sont contactées par l’intermédiaire des (hémato-), (neuro-) pédiatres, généticiens, registre A-T du CEREDIH (1), APRAT (2) et ORPHANET. Les femmes sont interrogées tous les deux ans sur leurs antécédents personnels et familiaux de cancer et sur leur exposition aux facteurs de risque de cancer. Le suivi médical proposé consiste en unesurveillance mammaire clinique, et si les femmes ont 40 ans et plus, une mammographie tous les deux ans. Une DNAthèque et une tumorothèque sont mises en place. Etat d’avancement Un peu plus de 4 ans après le début de l’étude, 182 familles A-T ont été identifiées à partir des dossiers médicaux du laboratoire de Génétique Oncologique de l’Institut Curie, dont 159 porteuses d’au moins une mutation identifiée. 513 femmes appartenant à 134 familles ont été invitées à participer ; 283 femmes (69 familles) ont accepté de participer. L’avancement de l’étude CoF-AT sera présenté en détail et les caractéristiques de la population incluse en janvier 2008 seront décrites. Remerciements Nous remercions vivement les femmes qui participent à cette étude ainsi que l’APRAT. CoF-AT est subventionnée par le Ministère de la Recherche et l’Inserm, la Fondation de France, le Conseil Scientifique de Radioprotection d’EDF, La Ligue Nationale Contre le Cancer. (1)Centre de Référence des Déficits Immunitaires Héréditaires (2)Association Pour la Recherche sur l’Ataxie-Télangiectasie
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- 2008
30. Etude de cohorte française sur l'ataxie-télangiectasie (CoF-AT) : 2003-2006
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Cavaciuti, Eve, Laugé, Anthony, d'Almeida, Alice, Labbé, Martine, Dondon, Marie-Gabrielle, Janin, Nicolas, Bay, Jacques-Olivier, Hall, Janet, Stoppa-Lyonnet, Dominique, Andrieu, Nadine, Méthodologie statistique et épidémiologie génétique des maladies multifactorielles, Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Génétique Oncologique, Institut Curie [Paris], Service de biostatistique (IC10213), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie [Paris], Département de génétique Humaine, CHU Sart Tilman, Unité de transplantation médullaire et laboratoire d'oncologie moléculaire, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER-UNICANCER, Groupe de la Réparation de l'ADN, CIRC, Groupe Cof-At, INSTITUT CURIE, Institut National de la Santé et de la Recherche Médicale (INSERM) - INSTITUT CURIE, CRLCC Jean Perrin, and Dondon, Marie-Gabrielle
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[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie - Abstract
National audience; L'Ataxie-Télangiectasie (AT) est une maladie génétique récessive de l'enfant caractérisée par une ataxie cérébelleuse dégénérative, des télangiectasies cutanées ou muqueuses,un déficit immunitaire et un risque augmenté de cancer. De plus, les mères d'enfants AT semblent avoir un risque élevé de cancer du sein (CS) comparé à celui de la population générale. En 1995 a été identifié un premier gène (ATM) responsable de cette maladie dont la protéine est impliquée dans la réparation des cassures double-brin de l'ADN. Bien que l'AT soit rare, jusqu'à 1% de la population pourrait être hétérozygote pour les gènes de l'AT. Ce trait génétique pourrait être impliqué dans un pourcentage non négligeable de CS. Les objectifs principaux de l'Etude CoF-AT sont, tout en proposant un suivi avec une action de dépistage précoce du CS, d'estimer le risque de cancer associé aux gènes de l'AT et d'étudier l'histoire naturelle du CS chez les hétérozygotes AT. Une cohorte de femmes apparentées au 1er, 2ème ou 3ième degré à un enfant AT est en cours de constitution depuis mai 2003. Ces femmes appartiennent aux familles recrutées lors de l'étude familiale rétrospective (1) et aux nouvelles familles identifiées dans le cadre des diagnostics des enfants atteints. Le contact auprès de ces dernières se fait par l'intermédiaire des pédiatres, des neuropédiatres, des généticiens et de l'APRAT (2). Un total de 800 inclusions de femmes hétérozygotes et non-hétérozygotes est attendu en 2 ans. Les femmes sont interrogées sur leurs antécédents personnels et familiaux de cancer et sur leur exposition aux facteurs de risque. Une DNAthèque et une tumorothèque sont mises en place. Un peu plus de 2 ans après le début de l'étude, environ 180 familles AT ont été identifiées à partir des dossiers médicaux du laboratoire de Génétique Oncologique de l'Institut Curie. 112 familles ont été invitées à participer, soit 371 femmes : 182 femmes appartenant à 57 familles différentes ont accepté de participer (49 %), 41 ont refusé (11 %), 148 n'ont pas encore répondu (40 %). L'avancement de l'étude CoF-AT sera présenté en détail et les caractéristiques de la population incluse en janvier 2006 seront décrites.
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- 2006
31. Causalité du gène ATM dans le développement d'un cancer du sein : tendance ou pas tendance ?
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D'Almeida, Alice, Cavaciuti, Eve, Dondon, Marie-Gabrielle, Laugé, Anthony, Janin, Nicolas, Stoppa-Lyonnet, Dominique, Andrieu, Nadine, Méthodologie statistique et épidémiologie génétique des maladies multifactorielles, Institut National de la Santé et de la Recherche Médicale (INSERM), Service de biostatistique (IC10213), Institut National de la Santé et de la Recherche Médicale (INSERM) - INSTITUT CURIE, Service de Génétique Oncologique, INSTITUT CURIE, Département de génétique Humaine, CHU Sart Tilman, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie [Paris], Institut Curie [Paris], and Dondon, Marie-Gabrielle
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[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie - Abstract
National audience; Objectifs : L'Ataxie télangiectasie (AT) est une maladie récessive de l'enfant caractérisée par une ataxie cérébelleuse dégénérative, des télangiectasies cutanées ou muqueuses, un déficit immunitaire et un risque augmenté de cancer. Des études sur les apparentés de patients AT ont montré que les femmes hétérozygotes AT (HetAT) ont un risque de cancer du sein (CS) multiplié par ~3 par rapport à la population générale. Cependant, la causalité des gènes de l'AT dans le CS est discutée : peu d'études en population générale (c'est-à-dire cas de CS non sélectionnés) de type cas témoin ou de cohorte ont observé une association entre le gène ATM et le CS (ex : FitzGerald et al., 1997) et aucune étude sur les apparentés de patients AT n'observe de tendance entre l'augmentation de la probabilité d'être porteur d'une mutation des gènes de l'AT et le risque de CS (J. Hall, 2005). Dans ce travail, nous nous sommes particulièrement intéressés à l'absence de tendance en explorant l'hypothèse qu'elle pouvait être partiellement expliquée par le mode de recensement des apparentés et par les méthodes utilisées pour déterminer leur statut vis-à-vis de la mutation ATM (statut ATM), méthodes pouvant a posteriori s'avérer plus ou moins biaisées. Données et méthodes : De 1994 à 1997, 34 familles ont été recensées à partir d'enfants AT. Les données démographiques, la survenue de cancer et les prélèvements sanguins ont été recueillis auprès des apparentés du 1er au 3e degré de l'enfant AT (Janin et al., 1999). Le nombre observé de cancers a été comparé au nombre attendu calculé à partir des données d'incidence estimées France entière. Trois méthodes ont été utilisées pour définir le statut ATM des individus : (1) l'approche « a priori » : le statut est déterminé par la probabilité d'être porteur de la mutation selon le degré de parenté avec l'enfant AT ; (2) l'approche « mixte » : le statut est déterminé par l'étude moléculaire ou en l'absence de prélèvement sanguin, calculé à partir du statut de l'apparenté testé le plus proche ; (3) l'approche « mixte corrigée » : afin d'éviter le biais potentiel dû au fait que seuls les survivants ont pu être testés, le statut d'un individu testé est déterminé par la probabilité a priori d'être porteur, le résultat de l'étude moléculaire servant alors à déterminer le statut de ses apparentés (Olsen et al., 2005). Résultats : Quelle que soit la méthode utilisée, on observe un risque relatif (RR) de CS élevé chez les HetAT. Ce RR est moins élevé mais plus précis avec l'approche « mixte » (RR = 3,88) qu'avec l'approche « a priori » (RR = 4,48) ou l'approche « mixte corrigée » (RR = 5,13). Le RR de CS est particulièrement élevé dans le groupe des mères (RR = 7,1), mais aussi dans le groupe des apparentées ayant une probabilité 0,125 d'être porteuse. Chez ces dernières, l'excès de risque semble être dû à un sur-échantillonnage de fratries éloignées lorsqu'un des membres de cette fratrie a un antécédent de cancer. En ignorant cette catégorie, le test de tendance est significatif avec les approches « a priori » (p = 0,012) et « mixte corrigée » (p = 0,048). Conclusion : Les méthodes utilisées pour déterminer le statut ATM modifient peu les estimations du RR de CS chez les HetAT. Par contre, la précision des estimations y est très sensible. La prise en compte des données moléculaires a clairement introduit un biais dû au sur-génotypage des cas de CS comparé aux apparentés non atteints. Ce biais se traduit par une sous estimation du risque de CS chez les apparentés au génotype incertain, expliquant l'absence de tendance initialement observée. Le test de tendance significatif observé en utilisant les méthodes « a priori » et « mixte corrigée » va dans le sens d'un lien de causalité entre ATM et CS. Le risque paraît plus élevé chez les mères que chez les autres HetAT mais les faibles effectifs ne permettent pas la mise en évidence d'une différence significative entre ces deux groupes. Des études à un échelon international permettront de préciser l'association entre ATM et CS.
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- 2006
32. Variation du risque de cancer du sein en fonction de la nature de la mutation du gène ATM. Étude familiale rétrospective
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Cavaciuti, Eve, Laugé, Anthony, Ossian, Katia, Janin, Nicolas, Hall, Janet, Stoppa-Lyonnet, Dominique, Andrieu, Nadine, Méthodologie statistique et épidémiologie génétique des maladies multifactorielles, Institut National de la Santé et de la Recherche Médicale (INSERM), Service de biostatistique (IC10213), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie [Paris], Service de Génétique Oncologique, Institut Curie [Paris], Institut Gustave Roussy (IGR), Département de génétique Humaine, CHU Sart Tilman, DNA Repair Group (CIRC), Centre international de recherche sur le cancer, Institut National de la Santé et de la Recherche Médicale (INSERM) - INSTITUT CURIE, INSTITUT CURIE, Dondon, Marie-Gabrielle, and Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)
- Subjects
[SDV.ETH] Life Sciences [q-bio]/Ethics ,[SDV.ETH]Life Sciences [q-bio]/Ethics - Abstract
Objectifs : L’ataxie-télangiectasie (AT) est une maladie récessive de l’enfant caractérisée par une ataxie cérébelleuse dégénérative, des télangiectasies cutanées ou muqueuses, un déficit immunitaire et un risque augmenté de cancer. Des études sur les familles AT ont montré que les femmes hétérozygotes AT (HetAT) ont un risque de cancer du sein (CS) multiplié par ~ 3 par rapport à la population générale. Bien que l’AT soit rare, jusqu’à 1 % de la population serait HetAT. Ce trait génétique pourrait donc être impliqué dans un pourcentage non négligeable de CS, entre 1 % et 3 %. Nous proposons d’estimer le risque de CS en fonction de la nature de la mutation du gène ATM et de la taille présumée des protéines ATM qui seraient produites à partir des allèles portant les mutations tronquantes.Méthodes : Entre 1994 et 1997, 34 familles (1 423 apparentés dont 711 femmes) ont été recensées à partir d’enfants AT. Les données démographiques, la survenue de cancer et les prélèvements sanguins ont été recueillis auprès des apparentés du 1er, 2e et 3e degré de l’enfant AT. Une mutation ATM a été identifiée dans 84 % des branches parentales explorées. Le nombre observé de cancers a été comparé au nombre attendu calculé à partir des données d’incidence estimées France entière.Résultats : Le risque de CS parmi les HetAT était multiplié par 3,96 par rapport à la population générale. Nous n’avons pas mis en évidence de différence de risque en fonction de la nature de la mutation (c’est-à-dire tronquantes vs « faux-sens »). L’étude de la variation du risque de CS en fonction de la longueur présumée de la protéine ATM tronquée met en évidence une association entre le risque de CS et la localisation de la mutation dans certains domaines du gène ATM.Conclusion : Bien que les conséquences biologiques des mutations tronquantes à l’état hétérozygote sur le processus de la réparation de l’ADN soit encore mal connue, ces résultats méritent d’être confirmés. En effet, si cette association est confirmée, la stratégie de dépistage du CS dans les familles AT pourrait être modifiée en fonction de la localisation de la mutation.
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- 2004
33. Les critères diagnostiques du syndrome de Lynch
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UCL - (SLuc) Centre de génétique médicale UCL, Janin, Nicolas, UCL - (SLuc) Centre de génétique médicale UCL, and Janin, Nicolas
- Abstract
Le syndrome de Lynch est décrit depuis longtemps et il est le plus fréquent des syndromes de prédisposition génétique au cancer du côlon, mais il reste très mal connu aujourd’hui. Deux raisons principales sont à l’origine de ce paradoxe : 1- le syndrome de Lynch a été décrit à une époque où la biologie particulière des cancers MSI-H n’était pas encore connue ; 2- la logique des critères d’Amsterdam a conduit à faire connaître le syndrome de Lynch d’une manière trompeuse, ne présentant presque pas les signes de la maladie pour ce qu’ils sont réellement, mais présentant en substance le syndrome de Lynch de manière négative par rapport à la polypose dominante. Le but de cette brève revue est de rectifier quelques-unes des idées fausses les plus répandues sur les aspects cliniques du syndrome de Lynch et donner quelques règles simples qui devraient permettre d’en faire facilement le diagnostic, The Lynch syndrome, which is the most common colon cancer predisposition syndrome, has been known for a long time. However, misconceptions about this disease remain widespread. Two main reasons account for this paradoxical situation: 1 - The Lynch syndrome was described long before the discovery of the MSI-H tumors' peculiar biology; 2-The rationale underlying the Amsterdam criteria led to presenting the Lynch syndrome in a distorted way, without addressing the disease's features for their own sake, but by explaining that the Lynch syndrome is not a dominant familial polyposis. Aim of this brief review is to settle right some of the most widespread misconceptions about the Lynch syndrome and to provide some simple rules that should enable an easy diagnosis of the disease
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- 2013
34. Identification of a new VHLexon and complex splicing alterations in familial erythrocytosis or von Hippel-Lindau disease
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Lenglet, Marion, Robriquet, Florence, Schwarz, Klaus, Camps, Carme, Couturier, Anne, Hoogewijs, David, Buffet, Alexandre, Knight, Samantha J.L., Gad, Sophie, Couvé, Sophie, Chesnel, Franck, Pacault, Mathilde, Lindenbaum, Pierre, Job, Sylvie, Dumont, Solenne, Besnard, Thomas, Cornec, Marine, Dreau, Helene, Pentony, Melissa, Kvikstad, Erika, Deveaux, Sophie, Burnichon, Nelly, Ferlicot, Sophie, Vilaine, Mathias, Mazzella, Jean-Michaël, Airaud, Fabrice, Garrec, Céline, Heidet, Laurence, Irtan, Sabine, Mantadakis, Elpis, Bouchireb, Karim, Debatin, Klaus-Michael, Redon, Richard, Bezieau, Stéphane, Bressac-de Paillerets, Brigitte, Teh, Bin Tean, Girodon, François, Randi, Maria-Luigia, Putti, Maria Caterina, Bours, Vincent, Van Wijk, Richard, Göthert, Joachim R., Kattamis, Antonis, Janin, Nicolas, Bento, Celeste, Taylor, Jenny C., Arlot-Bonnemains, Yannick, Richard, Stéphane, Gimenez-Roqueplo, Anne-Paule, Cario, Holger, and Gardie, Betty
- Abstract
Chuvash polycythemia is an autosomal recessive form of erythrocytosis associated with a homozygous p.Arg200Trp mutation in the von Hippel-Lindau (VHL) gene. Since this discovery, additional VHLmutations have been identified in patients with congenital erythrocytosis, in a homozygous or compound-heterozygous state. VHLis a major tumor suppressor gene, mutations in which were first described in patients presenting with VHL disease, which is characterized by the development of highly vascularized tumors. Here, we identify a new VHLcryptic exon (termed E1′) deep in intron 1 that is naturally expressed in many tissues. More importantly, we identify mutations in E1′ in 7 families with erythrocytosis (1 homozygous case and 6 compound-heterozygous cases with a mutation in E1′ in addition to a mutation in VHLcoding sequences) and in 1 large family with typical VHL disease but without any alteration in the other VHLexons. In this study, we show that the mutations induced a dysregulation of VHLsplicing with excessive retention of E1′ and were associated with a downregulation of VHL protein expression. In addition, we demonstrate a pathogenic role for synonymous mutations in VHLexon 2 that altered splicing through E2-skipping in 5 families with erythrocytosis or VHL disease. In all the studied cases, the mutations differentially affected splicing, correlating with phenotype severity. This study demonstrates that cryptic exon retention and exon skipping are new VHLalterations and reveals a novel complex splicing regulation of the VHLgene. These findings open new avenues for diagnosis and research regarding the VHL-related hypoxia-signaling pathway.
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- 2018
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35. The BRCA1c. 5096G>A p.Arg1699Gln (R1699Q) intermediate risk variant: breast and ovarian cancer risk estimation and recommendations for clinical management from the ENIGMA consortium
- Author
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Moghadasi, Setareh, Meeks, Huong D, Vreeswijk, Maaike PG, Janssen, Linda AM, Borg, Åke, Ehrencrona, Hans, Paulsson-Karlsson, Ylva, Wappenschmidt, Barbara, Engel, Christoph, Gehrig, Andrea, Arnold, Norbert, Hansen, Thomas Van Overeem, Thomassen, Mads, Jensen, Uffe Birk, Kruse, Torben A, Ejlertsen, Bent, Gerdes, Anne-Marie, Pedersen, Inge Søkilde, Caputo, Sandrine M, Couch, Fergus, Hallberg, Emily J, van den Ouweland, Ans MW, CollÅée, Margriet J, Teugels, Erik, Adank, Muriel A, van der Luijt, Rob B, Mensenkamp, Arjen R, Oosterwijk, Jan C, Blok, Marinus J, Janin, Nicolas, Claes, Kathleen BM, Tucker, Kathy, Viassolo, Valeria, Toland, Amanda Ewart, Eccles, Diana E, Devilee, Peter, Van Asperen, Christie J, Spurdle, Amanda B, Goldgar, David E, and GarcÅéóía, Encarna GÅéómez
- Abstract
BackgroundWe previously showed that the BRCA1variant c.5096G>A p.Arg1699Gln (R1699Q) was associated with an intermediate risk of breast cancer (BC) and ovarian cancer (OC). This study aimed to assess these cancer risks for R1699Q carriers in a larger cohort, including follow-up of previously studied families, to further define cancer risks and to propose adjusted clinical management of female BRCA1*R1699Q carriers.MethodsData were collected from 129 BRCA1*R1699Q families ascertained internationally by ENIGMA (Evidence-based Network for the Interpretation of Germline Mutant Alleles) consortium members. A modified segregation analysis was used to calculate BC and OC risks. Relative risks were calculated under both monogenic model and major gene plus polygenic model assumptions.ResultsIn this cohort the cumulative risk of BC and OC by age 70 years was 20% and 6%, respectively. The relative risk for developing cancer was higher when using a model that included the effects of both the R1699Q variant and a residual polygenic component compared with monogenic model (for BC 3.67 vs 2.83, and for OC 6.41 vs 5.83).ConclusionOur results confirm that BRCA1*R1699Q confers an intermediate risk for BC and OC. Breast surveillance for female carriers based on mammogram annually from age 40 is advised. Bilateral salpingo-oophorectomy should be considered based on family history.
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- 2018
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36. Germline PTPN11 missense mutation in a case of Noonan syndrome associated with mediastinal and retroperitoneal neuroblastic tumors
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Mutesa, Léon, Pierquin, Geneviève, Janin, Nicolas, Segers, Karin, Thomée, Caroline, Provenzi, Massimo, and Bours, Vincent
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- 2008
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37. Cancer predisposing missense and protein truncatingBARD1mutations in non-BRCA1orBRCA2breast cancer families
- Author
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De Brakeleer, Sylvia, primary, De Grève, Jacques, additional, Loris, Remy, additional, Janin, Nicolas, additional, Lissens, Willy, additional, Sermijn, Erica, additional, and Teugels, Erik, additional
- Published
- 2010
- Full Text
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38. Ataxia-Telangiectasia genes and breast cancer risk in a French family study
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Andrieu, Nadine, primary, Cavaciuti, Eve, additional, Laugé, Anthony, additional, Ossian, Katia, additional, Janin, Nicolas, additional, Hall, Janet, additional, and Stoppa-Lyonnet, Dominique, additional
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- 2005
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- View/download PDF
39. Variation in breast cancer risk of heterozygotes for ataxia-telangiectasia according to environmental factors
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Geoffroy-Perez, Béatrice, primary, Janin, Nicolas, additional, Ossian, Katia, additional, Laugé, Anthony, additional, Stoppa-Lyonnet, Dominique, additional, and Andrieu, Nadine, additional
- Published
- 2002
- Full Text
- View/download PDF
40. The R71GBRCA1is a founder Spanish mutation and leads to aberrant splicing of the transcript
- Author
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Vega, Ana, primary, Campos, Berta, additional, Bressac-de-Paillerets, Brigitte, additional, Bond, Patricia M., additional, Janin, Nicolas, additional, Douglas, Fiona S., additional, Domènech, Montserrat, additional, Baena, Manel, additional, Pericay, Carles, additional, Alonso, Carmen, additional, Carracedo, Angel, additional, Baiget, Montserrat, additional, and Diez, Orland, additional
- Published
- 2001
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- View/download PDF
41. Cancer risk in heterozygotes for ataxia-telangiectasia
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Geoffroy-Perez, B�atrice, primary, Janin, Nicolas, additional, Ossian, Katia, additional, Laug�, Anthony, additional, Croquette, Marie-Fran�oise, additional, Griscelli, Claude, additional, Debr�, Marianne, additional, Bressac-de-Paillerets, Brigitte, additional, Aurias, Alain, additional, Stoppa-Lyonnet, Dominique, additional, and Andrieu, Nadine, additional
- Published
- 2001
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- View/download PDF
42. Élucidation des énigmes du syndrome de Lynch grâce à un nouveau modèle de carcinogenèse caractérisé par un processus d'initiation hétérodoxe
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Janin, Nicolas, primary
- Published
- 1999
- Full Text
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43. Primary proliferative T cell response to wild‐type p53 protein in patients with breast cancer
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Tilkin, Anne‐Françoise, primary, Lubin, Richard, additional, Soussi, Thierry, additional, Lazar, Vladimir, additional, Janin, Nicolas, additional, Mathieu, Marie‐Christine, additional, Lefrère, Isabelle, additional, Carlu, Christiane, additional, Roy, Marguerite, additional, Kayibanda, Michèle, additional, Bellet, Dominique, additional, Guillet, Jean‐Gérard, additional, and Paillerets, Brigitte Bressac‐De, additional
- Published
- 1995
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44. A gene for Stargardt's disease (fundus flavimaculatus) maps to the short arm of chromosome 1
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Kaplan, Josseline, primary, Gerber, Sylvie, additional, Larget-Piet, Dominique, additional, Rozet, Jean-Michel, additional, Dollfus, Hélène, additional, Dufier, Jean-Louis, additional, Odent, Sylvie, additional, Postel-Vinay, Anne, additional, Janin, Nicolas, additional, Briard, Marie-Louise, additional, Frézal, Jean, additional, and Munnich, Arnold, additional
- Published
- 1993
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45. Cancer predisposing missense and protein truncating BARD1 mutations in non- BRCA1 or BRCA2 breast cancer families.
- Author
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De Brakeleer, Sylvia, De Grève, Jacques, Loris, Remy, Janin, Nicolas, Lissens, Willy, Sermijn, Erica, and Teugels, Erik
- Abstract
Fifteen years ago BRCA1 and BRCA2 were reported as high penetrant breast cancer predisposing genes. However, mutations in these genes are found in only a fraction of high risk families. BARD1 is a candidate breast cancer gene, but only a limited number of missense mutations with rather unclear pathogenic consequences have been reported.We screened 196 high risk breast cancer families for the occurrence of BARD1 variants. All genetic variants were analyzed using clinical information as well as IN SILICO predictive tools, including protein modeling. We found three candidate pathogenic mutations in seven families including a first case of a protein truncating mutation (p.Glu652fs) removing the entire second BRCT domain of BARD1. In conclusion, we provide evidence for an increased breast cancer risk associated to specific BARD1 germline mutations. However, these BARD1 mutations occur in a minority of hereditary breast cancer families. ©2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
46. Primary leptomeningeal melanoma is part of the BAP1-related cancer syndrome.
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Fouchardière, Arnaud, Cabaret, Odile, Pètre, Justine, Aydin, Selda, Leroy, Alice, Potter, Patrick, Pissaloux, Daniel, Haddad, Véronique, Bressac-de Paillerets, Brigitte, and Janin, Nicolas
- Subjects
BRAIN tumors ,INTRACRANIAL hypertension ,PATIENTS ,UBIQUITIN carboxy-terminal hydrolase ,METASTASIS ,HISTORY - Abstract
The article presents a case study of a 40-year-old woman with a supratentorial brain mass. It states that the patient recently suffered seizures. The patient died due to tumor compression-related intracranial hypertension 26 months she underwent initial surgery. The addition of the leptomeningeal melanoma to the list of tumors in mutated BAP1 carriers is also emphasized.
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- 2015
- Full Text
- View/download PDF
47. The R71G BRCA1 is a founder Spanish mutation and leads to aberrant splicing of the transcript.
- Author
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Vega, Ana, Campos, Berta, Bressac-de-Paillerets, Brigitte, Bond, Patricia M., Janin, Nicolas, Douglas, Fiona S., Domènech, Montserrat, Baena, Manel, Pericay, Carles, Alonso, Carmen, Carracedo, Angel, Baiget, Montserrat, and Diez, Orland
- Published
- 2001
- Full Text
- View/download PDF
48. The contribution of large genomic deletions at the CDKN2A locus to the burden of familial melanoma.
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Lesueur F, de Lichy M, Barrois M, Durand G, Bombled J, Avril MF, Chompret A, Boitier F, Lenoir GM, Bressac-de Paillerets B, Baccard M, Bachollet B, Berthet P, Bonadona V, Bonnetblanc JM, Caron O, Chevrant-Breton J, Cuny JF, Dalle S, Delaunay M, Demange L, De Quatrebarbes J, Doré JF, Frénay M, Fricker JP, Gauthier-Villars M, Gesta P, Giraud S, Gorry P, Grange F, Green A, Huiart L, Janin N, Joly P, Kérob D, Lasset C, Leroux D, Limacher JM, Longy M, Mansard S, Marrou K, Martin-Denavit T, Mateus C, Maubec E, Olivier-Faivre L, Orlandini V, Pujol P, Sassolas B, Stoppa-Lyonnet D, Thomas L, Vabres P, Venat L, Wierzbicka E, and Zattara H
- Subjects
- Aged, Aged, 80 and over, Base Sequence, Carrier Proteins genetics, Chromosomes, Human, Pair 9, Cyclin-Dependent Kinase Inhibitor p16 genetics, Exons, Female, Gene Deletion, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Molecular Sequence Data, Pedigree, Point Mutation, Reverse Transcriptase Polymerase Chain Reaction, Tumor Suppressor Protein p14ARF genetics, Genes, p16, Melanoma genetics
- Abstract
Mutations in two genes encoding cell cycle regulatory proteins have been shown to cause familial cutaneous malignant melanoma (CMM). About 20% of melanoma-prone families bear a point mutation in the CDKN2A locus at 9p21, which encodes two unrelated proteins, p16(INK4a) and p14(ARF). Rare mutations in CDK4 have also been linked to the disease. Although the CDKN2A gene has been shown to be the major melanoma predisposing gene, there remains a significant proportion of melanoma kindreds linked to 9p21 in which germline mutations of CDKN2A have not been identified through direct exon sequencing. The purpose of this study was to assess the contribution of large rearrangements in CDKN2A to the disease in melanoma-prone families using multiplex ligation-dependent probe amplification. We examined 214 patients from independent pedigrees with at least two CMM cases. All had been tested for CDKN2A and CDK4 point mutation, and 47 were found positive. Among the remaining 167 negative patients, one carried a novel genomic deletion of CDKN2A exon 2. Overall, genomic deletions represented 2.1% of total mutations in this series (1 of 48), confirming that they explain a very small proportion of CMM susceptibility. In addition, we excluded a new gene on 9p21, KLHL9, as being a major CMM gene.
- Published
- 2008
- Full Text
- View/download PDF
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