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85 results on '"Bressac-de Paillerets, Brigitte"'

1. The role of cancer predisposition syndrome in children and adolescents with very rare tumours

Author

Orbach, Daniel, Brecht, Ines B., Corradini, Nadege, Bouchoucha, Yassine, Roganovic, Jelena, Bourdeaut, Franck, Reguerre, Yves, Kuiper, Roland P., Bressac de Paillerets, Brigitte, Ferrari, Andrea, Virgone, Calogero, Godzinski, Jan, Bisogno, Gianni, Guerrini-Rousseau, Lea, Farinha, Nuno Jorge, Bergamaschi, Luca, Bien, Ewa, Kuhlen, Michaela, Schneider, Dominik T., and Ben Ami, Tal

Published
2023
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2. Biallelic Germline BRCA1 Frameshift Mutations Associated with Isolated Diminished Ovarian Reserve.

Author

Helbling-Leclerc, Anne, Falampin, Marie, Heddar, Abdelkader, Guerrini-Rousseau, Léa, Marchand, Maud, Cavadias, Iphigenie, Auger, Nathalie, Bressac-de Paillerets, Brigitte, Brugieres, Laurence, Lopez, Bernard S., Polak, Michel, Rosselli, Filippo, and Misrahi, Micheline

Abstract

The use of next-generation sequencing (NGS) has recently enabled the discovery of genetic causes of primary ovarian insufficiency (POI) with high genetic heterogeneity. In contrast, the causes of diminished ovarian reserve (DOR) remain poorly understood. Here, we identified by NGS and whole exome sequencing (WES) the cause of isolated DOR in a 14-year-old patient. Two frameshift mutations in BRCA1 (NM_007294.4) were found: in exon 8 (c.470_471del; p.Ser157Ter) and in exon 11 (c.791_794del, p.Ser264MetfsTer33). Unexpectedly, the patient presented no signs of Fanconi anemia (FA), i.e., no developmental abnormalities or indications of bone marrow failure. However, high chromosomal fragility was found in the patient's cells, consistent with an FA diagnosis. RT-PCR and Western-blot analysis support the fact that the c. 791_794del BRCA1 allele is transcribed and translated into a shorter protein (del11q), while no expression of the full-length BRCA1 protein was found. DNA damage response (DDR) studies after genotoxic agents demonstrate normal activation of the early stages of the DDR and FANC/BRCA pathway. This is consistent with the maintenance of residual repair activity for the del11q BRCA1 isoform. Our observation is the first implication of bi-allelic BRCA1 mutations in isolated ovarian dysfunction or infertility in humans, without clinical signs of FA, and highlights the importance of BRCA1 in ovarian development and function. [ABSTRACT FROM AUTHOR]

Published
2024
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3. Identification of a new VHL exon and complex splicing alterations in familial erythrocytosis or von Hippel-Lindau disease

Author

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

Published
2018
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4. Germline Variation at CDKN2A and Associations with Nevus Phenotypes among Members of Melanoma Families

Author

Taylor, Nicholas J., Mitra, Nandita, Goldstein, Alisa M., Tucker, Margaret A., Avril, Marie-Françoise, Azizi, Esther, Bergman, Wilma, Bishop, D. Timothy, Bressac-de Paillerets, Brigitte, Bruno, William, Calista, Donato, Cannon-Albright, Lisa A., Cuellar, Francisco, Cust, Anne E., Demenais, Florence, Elder, David E., Gerdes, Anne-Marie, Ghiorzo, Paola, Grazziotin, Thais C., Hansson, Johan, Harland, Mark, Hayward, Nicholas K., Hocevar, Marko, Höiom, Veronica, Ingvar, Christian, Landi, Maria Teresa, Landman, Gilles, Larre-Borges, Alejandra, Leachman, Sancy A., Mann, Graham J., Nagore, Eduardo, Olsson, Håkan, Palmer, Jane M., Perić, Barbara, Pjanova, Dace, Pritchard, Antonia, Puig, Susana, van der Stoep, Nienke, Wadt, Karin A.W., Whitaker, Linda, Yang, Xiaohong R., Newton Bishop, Julia A., Gruis, Nelleke A., and Kanetsky, Peter A.

Published
2017
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5. Guidelines for reporting secondary findings of genome sequencing in cancer genes: the SFMPP recommendations

Author

Pujol, Pascal, Vande Perre, Pierre, Faivre, Laurence, Sanlaville, Damien, Corsini, Carole, Baertschi, Bernard, Anahory, Michèle, Vaur, Dominique, Olschwang, Sylviane, Soufir, Nadem, Bastide, Noëlle, Amar, Sarah, Vintraud, Michèle, Ingster, Olivier, Richard, Stéphane, Le Coz, Pierre, Spano, Jean-Philippe, Caron, Olivier, Hammel, Pascal, Luporsi, Elisabeth, Toledano, Alain, Rebillard, Xavier, Cambon-Thomsen, Anne, Putois, Olivier, Rey, Jean-Marc, Hervé, Christian, Zorn, Caroline, Baudry, Karen, Galibert, Virginie, Gligorov, Joseph, Azria, David, Bressac-de Paillerets, Brigitte, Burnichon, Nelly, Spielmann, Marc, Zarca, Daniel, Coupier, Isabelle, Cussenot, Olivier, Gimenez-Roqueplo, Anne-Paule, Giraud, Sophie, Lapointe, Anne-Sophie, Niccoli, Patricia, Raingeard, Isabelle, Le Bidan, Muriel, Frebourg, Thierry, Rafii, Arash, and Geneviève, David

Published
2018
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6. Germline CDKN2A/P16INK4A mutations contribute to genetic determinism of sarcoma

Author

Jouenne, Fanélie, Chauvot de Beauchene, Isaure, Bollaert, Emeline, Avril, Marie-Françoise, Caron, Olivier, Ingster, Olivier, Lecesne, Axel, Benusiglio, Patrick, Terrier, Philippe, Caumette, Vincent, Pissaloux, Daniel, de la Fouchardière, Arnaud, Cabaret, Odile, N’Diaye, Birama, Velghe, Amélie, Bougeard, Gaelle, Mann, Graham J, Koscielny, Serge, Barrett, Jennifer H, Harland, Mark, Newton-Bishop, Julia, Gruis, Nelleke, Van Doorn, Remco, Gauthier-Villars, Marion, Pierron, Gaelle, Stoppa-Lyonnet, Dominique, Coupier, Isabelle, Guimbaud, Rosine, Delnatte, Capucine, Scoazec, Jean-Yves, Eggermont, Alexander M, Feunteun, Jean, Tchertanov, Luba, Demoulin, Jean-Baptiste, Frebourg, Thierry, and Bressac-de Paillerets, Brigitte

Published
2017
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7. The CDKN2A/p16INK4a 5′UTR sequence and translational regulation: impact of novel variants predisposing to melanoma

Author

Andreotti, Virginia, Bisio, Alessandra, Bressac-de Paillerets, Brigitte, Harland, Mark, Cabaret, Odile, Newton-Bishop, Julia, Pastorino, Lorenza, Bruno, William, Bertorelli, Roberto, De Sanctis, Veronica, Provenzani, Alessandro, Menin, Chiara, Fronza, Gilberto, Queirolo, Paola, Spitale, Robert C., Bianchi-Scarrà, Giovanna, Inga, Alberto, and Ghiorzo, Paola

Published
2016
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8. A germline mutation in PBRM1 predisposes to renal cell carcinoma

Author

Benusiglio, Patrick R, Couvé, Sophie, Gilbert-Dussardier, Brigitte, Deveaux, Sophie, Le Jeune, Hélène, Da Costa, Mélanie, Fromont, Gaëlle, Memeteau, Françoise, Yacoub, Mokrane, Coupier, Isabelle, Leroux, Dominique, Méjean, Arnaud, Escudier, Bernard, Giraud, Sophie, Gimenez-Roqueplo, Anne-Paule, Blondel, Christophe, Frouin, Eric, Teh, Bin T, Ferlicot, Sophie, Bressac-de Paillerets, Brigitte, Richard, Stéphane, and Gad, Sophie

Published
2015
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9. A SUMOylation-defective MITF germline mutation predisposes to melanoma and renal carcinoma

Author

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, Chaudru, Valérie, Lenoir, Gilbert M., Lathrop, Mark, Davidson, Irwin, Avril, Marie-Françoise, Demenais, Florence, Ballotti, Robert, and Bressac-de Paillerets, Brigitte

Published
2011
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11. Germline Mutations of Inhibins in Early-Onset Ovarian Epithelial Tumors

Author

Tournier, Isabelle, Marlin, Régine, Walton, Kelly, Charbonnier, Françoise, Coutant, Sophie, Théry, Jean-Christophe, Charbonnier, Camille, Spurrell, Cailyn, Vezain, Myriam, Ippolito, Lorena, Bougeard, Gaëlle, Roman, Horace, Tinat, Julie, Sabourin, Jean-Christophe, Stoppa-Lyonnet, Dominique, Caron, Olivier, Bressac-de Paillerets, Brigitte, Vaur, Dominique, King, Mary-Claire, Harrison, Craig, and Frebourg, Thierry

Published
2014
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13. Melanoma prone families with CDK4 germline mutation: phenotypic profile and associations with MC1R variants

Author

Puntervoll, Hanne Eknes, Yang, Xiaohong R, Vetti, Hildegunn Høberg, Bachmann, Ingeborg M, Avril, Marie Françoise, Benfodda, Meriem, Catricalà, Caterina, Dalle, Stéphane, Duval-Modeste, Anne B, Ghiorzo, Paola, Grammatico, Paola, Harland, Mark, Hayward, Nicholas K, Hu, Hui-Han, Jouary, Thomas, Martin-Denavit, Tanguy, Ozola, Aija, Palmer, Jane M, Pastorino, Lorenza, Pjanova, Dace, Soufir, Nadem, Steine, Solrun J, Stratigos, Alexander J, Thomas, Luc, Tinat, Julie, Tsao, Hensin, Veinalde, Rūta, Tucker, Margaret A, Bressac-de Paillerets, Brigitte, Newton-Bishop, Julia A, Goldstein, Alisa M, Akslen, Lars A, and Molven, Anders

Published
2013
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14. Tracking of Second Primary Melanomas in Vemurafenib-Treated Patients

Author

Dalle, Stephane, Poulalhon, Nicolas, Debarbieux, Sébastien, Zaharia, Daniela, Mihm, Martin C., Lacouture, Mario E., Rosen, Alyx, Marghoob, Ashfaq A., Busam, Klaus J., Depaepe, Lauriane, Bringuier, Pierre-Paul, Richez, Pauline, Baurain, Jean-François, Bressac–de Paillerets, Brigitte, Balme, Brigitte, and Thomas, Luc

Published
2013
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15. Localization of a novel melanoma susceptibility locus to 1p22

Author

Gillanders, Elizabeth, Juo, Suh-Hang Hank, Holland, Elizabeth A., Jones, MaryPat, Nancarrow, Derek, Freas-Lutz, Diana, Sood, Raman, Park, Naeun, Faruque, Mezbah, Markey, Carol, Kefford, Richard F., Palmer, Jane, Bergman, Wilma, Bishop, D. Timothy, Tucker, Margaret A., Bressac-de Paillerets, Brigitte, Hansson, Johan, Stark, Mitchell, Gruis, Nelleke, Bishop, Julia Newton, Goldstein, Alisa M., Bailey-Wilson, Joan E., Mann, Graham J., Hayward, Nicholas, and Trent, Jeffrey

Subjects
Melanoma -- Research, Biological sciences
Published
2003

16. Guidelines for splicing analysis in molecular diagnosis derived from a set of 327 combined in silico/in vitro studies on BRCA1 and BRCA2 variants

Author

Houdayer, Claude, Caux-Moncoutier, Virginie, Krieger, Sophie, Barrois, Michel, Bonnet, Françoise, Bourdon, Violaine, Bronner, Myriam, Buisson, Monique, Coulet, Florence, Gaildrat, Pascaline, Lefol, Cédrick, Léone, Mélanie, Mazoyer, Sylvie, Muller, Danielle, Remenieras, Audrey, Révillion, Françoise, Rouleau, Etienne, Sokolowska, Joanna, Vert, Jean-Philippe, Lidereau, Rosette, Soubrier, Florent, Sobol, Hagay, Sevenet, Nicolas, Bressac-de Paillerets, Brigitte, Hardouin, Agnès, Tosi, Mario, Sinilnikova, Olga M., and Stoppa-Lyonnet, Dominique

Published
2012
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17. Common variants of the BRCA1 wild-type allele modify the risk of breast cancer in BRCA1 mutation carriers

Author

Cox, David G., Simard, Jacques, Sinnett, Daniel, Hamdi, Yosr, Soucy, Penny, Ouimet, Manon, Barjhoux, Laure, Verny-Pierre, Carole, McGuffog, Lesley, Healey, Sue, Szabo, Csilla, Greene, Mark H., Mai, Phuong L., Andrulis, Irene L., Thomassen, Mads, Gerdes, Anne-Marie, Caligo, Maria A., Friedman, Eitan, Laitman, Yael, Kaufman, Bella, Paluch, Shani S., Borg, Åke, Karlsson, Per, Stenmark Askmalm, Marie, Barbany Bustinza, Gisela, Nathanson, Katherine L., Domchek, Susan M., Rebbeck, Timothy R., Benítez, Javier, Hamann, Ute, Rookus, Matti A., van den Ouweland, Ans M.W., Ausems, Margreet G.E.M., Aalfs, Cora M., van Asperen, Christi J., Devilee, Peter, Gille, Hans J.J.P., Peock, Susan, Frost, Debra, Evans, D. Gareth, Eeles, Ros, Izatt, Louise, Adlard, Julian, Paterson, Joan, Eason, Jacqueline, Godwin, Andrew K., Remon, Marie-Alice, Moncoutier, Virginie, Gauthier-Villars, Marion, Lasset, Christine, Giraud, Sophie, Hardouin, Agnès, Berthet, Pascaline, Sobol, Hagay, Eisinger, François, Bressac de Paillerets, Brigitte, Caron, Olivier, Delnatte, Capucine, Goldgar, David, Miron, Alex, Ozcelik, Hilmi, Buys, Saundra, Southey, Melissa C., Terry, Mary Beth, Singer, Christian F., Dressler, Anne-Catharina, Tea, Muy-Kheng, Hansen, Thomas V.O., Johannsson, Oskar, Piedmonte, Marion, Rodriguez, Gustavo C., Basil, Jack B., Blank, Stephanie, Toland, Amanda E., Montagna, Marco, Isaacs, Claudine, Blanco, Ignacio, Gayther, Simon A., Moysich, Kirsten B., Schmutzler, Rita K., Wappenschmidt, Barbara, Engel, Christoph, Meindl, Alfons, Ditsch, Nina, Arnold, Norbert, Niederacher, Dieter, Sutter, Christian, Gadzicki, Dorothea, Fiebig, Britta, Caldes, Trinidad, Laframboise, Rachel, Nevanlinna, Heli, Chen, Xiaoqing, Beesley, Jonathan, Spurdle, Amanda B., Neuhausen, Susan L., Ding, Yuan C., Couch, Fergus J., Wang, Xianshu, Peterlongo, Paolo, Manoukian, Siranoush, Bernard, Loris, Radice, Paolo, Easton, Douglas F., Chenevix-Trench, Georgia, Antoniou, Antonis C., Stoppa-Lyonnet, Dominique, Mazoyer, Sylvie, and Sinilnikova, Olga M.

Published
2011
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18. Common variants in LSP1, 2q35 and 8q24 and breast cancer risk for BRCA1 and BRCA2 mutation carriers

Author

Antoniou, Antonis C., Sinilnikova, Olga M., McGuffog, Lesley, Healey, Sue, Nevanlinna, Heli, Heikkinen, Tuomas, Simard, Jacques, Spurdle, Amanda B., Beesley, Jonathan, Chen, Xiaoqing, Neuhausen, Susan L., Ding, Yuan C., Couch, Fergus J., Wang, Xianshu, Fredericksen, Zachary, Peterlongo, Paolo, Peissel, Bernard, Bonanni, Bernardo, Viel, Alessandra, Bernard, Loris, Radice, Paolo, Szabo, Csilla I., Foretova, Lenka, Zikan, Michal, Claes, Kathleen, Greene, Mark H., Mai, Phuong L., Rennert, Gad, Lejbkowicz, Flavio, Andrulis, Irene L., Ozcelik, Hilmi, Glendon, Gord, Gerdes, Anne-Marie, Thomassen, Mads, Sunde, Lone, Caligo, Maria A., Laitman, Yael, Kontorovich, Tair, Cohen, Shimrit, Kaufman, Bella, Dagan, Efrat, Baruch, Ruth Gershoni, Friedman, Eitan, Harbst, Katja, Barbany-Bustinza, Gisela, Rantala, Johanna, Ehrencrona, Hans, Karlsson, Per, Domchek, Susan M., Nathanson, Katherine L., Osorio, Ana, Blanco, Ignacio, Lasa, Adriana, Benítez, Javier, Hamann, Ute, Hogervorst, Frans B.L., Rookus, Matti A., Collee, J Margriet, Devilee, Peter, Ligtenberg, Marjolijn J., van der Luijt, Rob B., Aalfs, Cora M., Waisfisz, Quinten, Wijnen, Juul, van Roozendaal, Cornelis E.P., Peock, Susan, Cook, Margaret, Frost, Debra, Oliver, Clare, Platte, Radka, Evans, D Gareth, Lalloo, Fiona, Eeles, Rosalind, Izatt, Louise, Davidson, Rosemarie, Chu, Carol, Eccles, Diana, Cole, Trevor, Hodgson, Shirley, Godwin, Andrew K., Stoppa-Lyonnet, Dominique, Buecher, Bruno, Léoné, Mélanie, Bressac-de Paillerets, Brigitte, Remenieras, Audrey, Caron, Olivier, Lenoir, Gilbert M., Sevenet, Nicolas, Longy, Michel, Ferrer, Sandra Fert, Prieur, Fabienne, Goldgar, David, Miron, Alexander, John, Esther M., Buys, Saundra S., Daly, Mary B., Hopper, John L., Terry, Mary Beth, Yassin, Yosuf, Gschwantler-Kaulich, Daphne, Staudigl, Christine, Hansen, Thomas v. O., Barkardottir, Rosa Bjork, Kirchhoff, Tomas, Pal, Prodipto, Kosarin, Kristi, Offit, Kenneth, Piedmonte, Marion, Rodriguez, Gustavo C., Wakeley, Katie, Boggess, John F., Basil, Jack, Schwartz, Peter E., Blank, Stephanie V., Toland, Amanda E., Montagna, Marco, Casella, Cinzia, Imyanitov, Evgeny N., Allavena, Anna, Schmutzler, Rita K., Versmold, Beatrix, Engel, Christoph, Meindl, Alfons, Ditsch, Nina, Arnold, Norbert, Niederacher, Dieter, Deiler, Helmut, Fiebig, Britta, Suttner, Christian, Schönbuchner, Ines, Gadzicki, Dorothea, Caldes, Trinidad, de la Hoya, Miguel, Pooley, Karen A., Easton, Douglas F., and Chenevix-Trench, Georgia

Published
2009

19. Novel germline MET pathogenic variants in French patients with papillary renal cell carcinomas type I.

Author

Sebai, Molka, Tulasne, David, Caputo, Sandrine M., Verkarre, Virginie, Fernandes, Marie, Guérin, Célia, Reinhart, Fanny, Adams, Séverine, Maugard, Christine, Caron, Olivier, Guillaud‐Bataille, Marine, Berthet, Pascaline, Bignon, Yves‐Jean, Bressac‐de Paillerets, Brigitte, Burnichon, Nelly, Chiesa, Jean, Giraud, Sophie, Lejeune, Sophie, Limacher, Jean‐Marc, and de Pauw, Antoine

Abstract

Hereditary papillary renal cell carcinoma (HPRC) is a rare inherited renal cancer syndrome characterized by bilateral and multifocal papillary type 1 renal tumors (PRCC1). Activating germline pathogenic variants of the MET gene were identified in HPRC families. We reviewed the medical and molecular records of a large French series of 158 patients screened for MET oncogenic variants. MET pathogenic and likely pathogenic variants rate was 12.4% with 40.6% among patients with familial PRCC1 and 5% among patients with sporadic PRCC1. The phenotype in cases with MET pathogenic and likely pathogenic variants was characteristic: PRCC1 tumors were mainly bilateral (84.3%) and multifocal (87.5%). Histologically, six out of seven patients with MET pathogenic variant harbored biphasic squamoid alveolar PRCC. Genetic screening identified one novel pathogenic variant MET c.3389T>C, p.(Leu1130Ser) and three novel likely pathogenic variants: MET c.3257A>T, p.(His1086Leu); MET c.3305T>C, p.(Ile1102Thr) and MET c.3373T>G, p.(Cys1125Gly). Functional assay confirmed their oncogenic effect as they induced an abnormal focus formation. The genotype–phenotype correlation between MET pathogenic variants and PRCC1 presentation should encourage to widen the screening, especially toward nonfamilial PRCC1. This precise phenotype also constitutes a strong argument for the classification of novel missense variants within the tyrosine kinase domain when functional assays are not accessible. [ABSTRACT FROM AUTHOR]

Published
2022
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20. Corrigendum: A SUMOylation-defective MITF germline mutation predisposes to melanoma and renal carcinoma

Author

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; [...]

Published
2016
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21. Genetic Testing in Pheochromocytoma or Functional Paraganglioma

Author

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

Published
2005
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22. Breast cancer risk in BRCA1 and BRCA2 mutation carriers and polyglutamine repeat length in the AIB1 gene

Author

Hughes, David J., Ginolhac, Sophie M., Coupier, Isabelle, Barjhoux, Laure, Gaborieau, Valérie, Bressac-de-Paillerets, Brigitte, Chompret, Agnès, Bignon, Yves-Jean, Uhrhammer, Nancy, Lasset, Christine, Giraud, Sophie, Sobol, Hagay, Hardouin, Agnès, Berthet, Pascaline, Peyrat, Jean-Philippe, Fournier, Joelle, Nogues, Catherine, Lidereau, Rosette, Muller, Danièle, Fricker, Jean-Pierre, Longy, Michel, Toulas, Christine, Guimbaud, Rosine, Yannoukakos, Drakoulis, Mazoyer, Sylvie, Lynch, Henry T., Lenoir, Gilbert M., Goldgar, David E., Stoppa-Lyonnet, Dominique, and Sinilnikova, Olga M.

Published
2005
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24. Familial melanoma: Clinical factors associated with germline CDKN2A mutations according to the number of patients affected by melanoma in a family

Author

Maubec, Eve, Chaudru, Valérie, Mohamdi, Hamida, Blondel, Christophe, Margaritte-Jeannin, Patricia, Forget, Sébastien, Corda, Eve, Boitier, Françoise, Dalle, Stéphane, Vabres, Pierre, Perrot, Jean-Luc, Lyonnet, Dominique Stoppa, Zattara, Hélène, Mansard, Sandrine, Grange, Florent, Leccia, Marie-Thérèse, Vincent-Fetita, Lynda, Martin, Ludovic, Crickx, Béatrice, Joly, Pascal, Thomas, Luc, Bressac-de Paillerets, Brigitte, Avril, Marie-Françoise, and Demenais, Florence

Published
2012
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25. A new hybrid record linkage process to make epidemiological databases interoperable: application to the GEMO and GENEPSO studies involving BRCA1 and BRCA2 mutation carriers.

Author

Jiao, Yue, Lesueur, Fabienne, Azencott, Chloé-Agathe, Laurent, Maïté, Mebirouk, Noura, Laborde, Lilian, Beauvallet, Juana, Dondon, Marie-Gabrielle, Eon-Marchais, Séverine, Laugé, Anthony, GEMO Study Collaborators, Boutry-Kryza, Nadia, Calender, Alain, Giraud, Sophie, Léone, Mélanie, Bressac-de-Paillerets, Brigitte, Caron, Olivier, Guillaud-Bataille, Marine, Bignon, Yves-Jean, and Uhrhammer, Nancy

Subjects
SUPERVISED learning, BRCA genes, DISEASE risk factors, SUPPORT vector machines, ALGORITHMS, MEDICAL registries
Abstract

Background: Linking independent sources of data describing the same individuals enable innovative epidemiological and health studies but require a robust record linkage approach. We describe a hybrid record linkage process to link databases from two independent ongoing French national studies, GEMO (Genetic Modifiers of BRCA1 and BRCA2), which focuses on the identification of genetic factors modifying cancer risk of BRCA1 and BRCA2 mutation carriers, and GENEPSO (prospective cohort of BRCAx mutation carriers), which focuses on environmental and lifestyle risk factors.Methods: To identify as many as possible of the individuals participating in the two studies but not registered by a shared identifier, we combined probabilistic record linkage (PRL) and supervised machine learning (ML). This approach (named "PRL + ML") combined together the candidate matches identified by both approaches. We built the ML model using the gold standard on a first version of the two databases as a training dataset. This gold standard was obtained from PRL-derived matches verified by an exhaustive manual review. Results The Random Forest (RF) algorithm showed a highest recall (0.985) among six widely used ML algorithms: RF, Bagged trees, AdaBoost, Support Vector Machine, Neural Network. Therefore, RF was selected to build the ML model since our goal was to identify the maximum number of true matches. Our combined linkage PRL + ML showed a higher recall (range 0.988-0.992) than either PRL (range 0.916-0.991) or ML (0.981) alone. It identified 1995 individuals participating in both GEMO (6375 participants) and GENEPSO (4925 participants).Conclusions: Our hybrid linkage process represents an efficient tool for linking GEMO and GENEPSO. It may be generalizable to other epidemiological studies involving other databases and registries. [ABSTRACT FROM AUTHOR]

Published
2021
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26. Selection criteria for genetic assessment of patients with familial melanoma

Author

Leachman, Sancy A., Carucci, John, Kohlmann, Wendy, Banks, Kimberly C., Asgari, Maryam M., Bergman, Wilma, Bianchi-Scarrà, Giovanna, Brentnall, Teresa, Bressac-de Paillerets, Brigitte, Bruno, William, Curiel-Lewandrowski, Clara, de Snoo, Femke A., Debniak, Tadeusz, Demierre, Marie-France, Elder, David, Goldstein, Alisa M., Grant-Kels, Jane, Halpern, Allan C., Ingvar, Christian, Kefford, Richard F., Lang, Julie, MacKie, Rona M., Mann, Graham J., Mueller, Kurt, Newton-Bishop, Julia, Olsson, Håkan, Petersen, Gloria M., Puig, Susana, Rigel, Darrell, Swetter, Susan M., Tucker, Margaret A., Yakobson, Emanuel, Zitelli, John A., and Tsao, Hensin

Published
2009
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27. Melanoma Risk and Melanocyte Biology.

Author

BERTRAND, Juliette U., STEINGRIMSSON, Eirikur, JOUENNE, Fanélie, BRESSAC-DE PAILLERETS, Brigitte, and LARUE, Lionel

Subjects
MELANOMA, BIOLOGICAL pigments, BIOLOGY, NUCLEOTIDE sequencing, CYTOLOGY, DYSPLASTIC nevus syndrome
Abstract

Cutaneous melanoma arises from melanocytes following genetic, epigenetic and allogenetic (i.e. other than epi/genetic) modifications. An estimated 10% of cutaneous melanoma cases are due to inherited variants or de novo mutations in approximately 20 genes, found using linkage, next-generation sequencing and association studies. Based on these studies, 3 classes of predisposing melanoma genes have been defined based on the frequency of the variants in the general population and lifetime risk of developing a melanoma: (i) ultra-rare variants with a high risk, (ii) rare with a moderate risk, and (iii) frequent variants with a low risk. Most of the proteins encoded by these genes have been shown to be involved in melanoma initiation, including proliferation and senescence bypass. This paper reviews the role(s) of these genes in the transformation of melanocytes into melanoma. It also describes their function in the establishment and renewal of melanocytes and the biology of pigment cells, if known. [ABSTRACT FROM AUTHOR]

Published
2020
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28. Estimating CDKN2A mutation carrier probability among global familial melanoma cases using GenoMELPREDICT.

Author

Taylor, Nicholas J., Mitra, Nandita, Qian, Lu, Avril, Marie-Françoise, Bishop, D. Timothy, Bressac-de Paillerets, Brigitte, Bruno, William, Calista, Donato, Cuellar, Francisco, Cust, Anne E., Demenais, Florence, Elder, David E., Gerdes, Anne-Marie, Ghiorzo, Paola, Goldstein, Alisa M., Grazziotin, Thais C., Gruis, Nelleke A., Hansson, Johan, Harland, Mark, and Hayward, Nicholas K.

Abstract

Background: Although rare in the general population, highly penetrant germline mutations in CDKN2A are responsible for 5%-40% of melanoma cases reported in melanoma-prone families. We sought to determine whether MELPREDICT was generalizable to a global series of families with melanoma and whether performance improvements can be achieved.Methods: In total, 2116 familial melanoma cases were ascertained by the international GenoMEL Consortium. We recapitulated the MELPREDICT model within our data (GenoMELPREDICT) to assess performance improvements by adding phenotypic risk factors and history of pancreatic cancer. We report areas under the curve (AUC) with 95% confidence intervals (CIs) along with net reclassification indices (NRIs) as performance metrics.Results: MELPREDICT performed well (AUC 0.752, 95% CI 0.730-0.775), and GenoMELPREDICT performance was similar (AUC 0.748, 95% CI 0.726-0.771). Adding a reported history of pancreatic cancer yielded discriminatory improvement (P < .0001) in GenoMELPREDICT (AUC 0.772, 95% CI 0.750-0.793, NRI 0.40). Including phenotypic risk factors did not improve performance.Conclusion: The MELPREDICT model functioned well in a global data set of familial melanoma cases. Adding pancreatic cancer history improved model prediction. GenoMELPREDICT is a simple tool for predicting CDKN2A mutational status among melanoma patients from melanoma-prone families and can aid in directing these patients to receive genetic testing or cancer risk counseling. [ABSTRACT FROM AUTHOR]

Published
2019
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29. Association of the POT1 Germline Missense Variant p.I78T With Familial Melanoma.

Author

Wong, Kim, Robles-Espinoza, Carla Daniela, Rodriguez, David, Rudat, Saskia S., Puig, Susana, Potrony, Miriam, Wong, Chi C., Hewinson, James, Aguilera, Paula, Puig-Butille, Joan Anton, Bressac-de Paillerets, Brigitte, Zattara, Hélène, van der Weyden, Louise, Fletcher, Christopher D. M., Brenn, Thomas, Arends, Mark J., Quesada, Víctor, Newton-Bishop, Julia A., Lopez-Otin, Carlos, and Bishop, D. Timothy

Published
2019
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30. A Single Genetic Origin for the G101W CDKN2A Mutation in 20 Melanoma-Prone Families

Author

Ciotti, Paola, Struewing, Jeffery P., Mantelli, Michela, Chompret, Agnes, Avril, Marie-Francoise, Santi, Pier Luigi, Tucker, Margaret A., Bianchi-Scarra, Giovanna, Bressac-de Paillerets, Brigitte, and Goldstein, Alisa M.

Subjects
Heredity, Human -- Research, Melanoma -- Genetic aspects, Familial diseases -- Genetic aspects, Mutation (Biology) -- Health aspects, Genetic disorders -- Research, Biological sciences
Published
2000

31. Integrative analysis of dysregulated microRNAs and mRNAs in multiple recurrent synchronized renal tumors from patients with von Hippel-Lindau disease.

Author

Gattolliat, Charles-Henry, Couvé, Sophie, Meurice, Guillaume, Oréar, Cédric, Droin, Nathalie, Chiquet, Mathieu, Ferlicot, Sophie, Verkarre, Virginie, Vasiliu, Viorel, Molinié, Vincent, Méjean, Arnaud, Dessen, Philippe, Giraud, Sophie, Bressac-De-Paillerets, Brigitte, Gardie, Betty, Teh, Bin Tean, Richard, Stéphane, and Gad, Sophie

Published
2018
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32. Contribution of de novo and mosaic TP53 mutations to Li-Fraumeni syndrome.

Author

Renaux-Petel, Mariette, Charbonnier, Françoise, Théry, Jean-Christophe, Fermey, Pierre, Lienard, Gwendoline, Bou, Jacqueline, Coutant, Sophie, Vezain, Myriam, Kasper, Edwige, Fourneaux, Steeve, Manase, Sandrine, Blanluet, Maud, Leheup, Bruno, Mansuy, Ludovic, Champigneulle, Jacqueline, Chappé, Céline, Longy, Michel, Sévenet, Nicolas, Bressac-de Paillerets, Brigitte, and Guerrini-Rousseau, Léa

Abstract

Background: Development of tumours such as adrenocortical carcinomas (ACC), choroid plexus tumours (CPT) or female breast cancers before age 31 or multiple primary cancers belonging to the Li-Fraumeni (LFS) spectrum is, independently of the familial history, highly suggestive of a germline TP53 mutation. The aim of this study was to determine the contribution of de novo and mosaic mutations to LFS. Methods and results: A mong 328 unrelated patients harbouring a germline TP53 mutation identified by Sanger sequencing and/or QMPSF, we could show that the mutations had occurred de novo in 40 cases, without detectable parental age effect. Sanger sequencing revealed two mosaic mutations in a child with ACC and in an unaffected father of a child with medulloblastoma. Re-analysis of blood DNA by next-generation sequencing, performed at a depth above 500X, from 108 patients suggestive of LFS without detectable TP53 mutations, allowed us to identify 6 additional cases of mosaic TP53 mutations, in 2/49 children with ACC, 2/21 children with CPT, in 1/31 women with breast cancer before age 31 and in a patient who developed an osteosarcoma at age 12, a breast carcinoma and a breast sarcoma at age 35. Conclusions: This study performed on a large series of TP53 mutation carriers allows estimating the contribution to LFS of de novo mutations to at least 14% (48/336) and suggests that approximately onefifth of these de novo mutations occur during embryonic development. Considering the medical impact of TP53 mutation identification, medical laboratories in charge of TP53 testing should ensure the detection of mosaic mutations. [ABSTRACT FROM AUTHOR]

Published
2018
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35. PARKIN Inactivation Links Parkinson's Disease to Melanoma.

Author

Hui-Han Hu, Kannengiesser, Caroline, Lesage, Suzanne, André, Jocelyne, Mourah, Samia, Michel, Laurence, Descamps, Vincent, Basset-Seguin, Nicole, Bagot, Martine, Bensussan, Armand, Lebbé, Céleste, Deschamps, Lydia, Saiag, Philippe, Leccia, Marie-Thérèse, Bressac-de-Paillerets, Brigitte, Tsalamlal, Amel, Kumar, Rajiv, Klebe, Stephan, Grandchamp, Bernard, and Andrieu-Abadie, Nathalie

Subjects
PROTEIN metabolism, DNA analysis, ENZYME metabolism, CELL lines, CELL physiology, ENZYMES, EPITHELIAL cells, GENES, GENETICS, MELANOMA, GENETIC mutation, PARKINSON'S disease, PROTEINS, SKIN tumors, WESTERN immunoblotting, RELATIVE medical risk, CASE-control method, SEQUENCE analysis, ODDS ratio, GENOTYPES
Abstract

Background: Melanoma incidence is higher in patients affected by Parkinson's disease (PD) and vice versa, but the genetic link shared by both diseases is unknown. As PARK2 is both a tumor suppressor gene and frequently mutated in young onset PD, we evaluated the role of PARK2 in melanoma predisposition and progression.Methods: An in-depth PARK2 gene dosage analysis and sequencing was performed on 512 French case patients and 562 healthy control patients, as well as sporadic tumors and melanoma cell lines. The frequency of genetic alterations was compared between case patients and control patients using two-sided Fisher's exact tests and odds ratio (OR) calculations. We used western blotting to determine PARKIN expression in melanocytes and melanoma cell lines and transfection followed by clonogenic assays to evaluate the effect of PARKIN expression on cellular proliferation. All statistical tests were two-sided.Results: Germline PARK2 mutations (including copy number variations, splicing, and putative deleterious missense mutations) were present in 25 case patients but only four control patients (OR = 3.95, 95% confidence interval = 1.34 to 15.75). Copy number variations (CNVs) and loss of heterozygosity were present in 60% and 74%, respectively, of primary tumors. PARKIN protein was expressed in melanocytes but not in most melanoma cell lines, and its expression decreased following melanocyte transformation by oncogenic NRAS. Re-expression of PARKIN in melanoma cell lines resulted in a drastic reduction of cell proliferation and inhibition of PARKIN in melanocytes stimulated their proliferation.Conclusion: Our results show an important role for PARK2 as a tumor suppressor both in melanoma predisposition and progression, which could explain the epidemiological association of these diseases. [ABSTRACT FROM AUTHOR]

Published
2016
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36. The CDKN2A/p16 INK 4a 5′ UTR sequence and translational regulation: impact of novel variants predisposing to melanoma.

Author

Andreotti, Virginia, Bisio, Alessandra, Bressac ‐ de Paillerets, Brigitte, Harland, Mark, Cabaret, Odile, Newton ‐ Bishop, Julia, Pastorino, Lorenza, Bruno, William, Bertorelli, Roberto, De Sanctis, Veronica, Provenzani, Alessandro, Menin, Chiara, Fronza, Gilberto, Queirolo, Paola, Spitale, Robert C., Bianchi ‐ Scarrà, Giovanna, Inga, Alberto, and Ghiorzo, Paola

Subjects
CANCER genetics, WESTERN immunoblotting, ALLELES, GENETIC mutation, MESSENGER RNA
Abstract

Many variants of uncertain functional significance in cancer susceptibility genes lie in regulatory regions, and clarifying their association with disease risk poses significant challenges. We studied 17 germline variants (nine of which were novel) in the CDKN2A 5′ UTR with independent approaches, which included mono and bicistronic reporter assays, Western blot of endogenous protein, and allelic representation after polysomal profiling to investigate their impact on CDKN2A mRNA translation regulation. Two of the novel variants (c.-27del23, c.-93-91del AGG) were classified as causal mutations (score ≥3), along with the c.-21C>T, c.-34G>T, and c.-56G>T, which had already been studied by a subset of assays. The novel c.-42T>A as well as the previously described c.-67G>C were classified as potential mutations (score 1 or 2). The remaining variants (c.-14C>T, c.-20A>G, c.-25C>T+c.-180G>A, c.-30G>A, c.-40C>T, c.-45G>A, c.-59C>G, c.-87T>A, c.-252A>T) were classified as neutral (score 0). In conclusion, we found evidence that nearly half of the variants found in this region had a negative impact on CDKN2A mRNA translation, supporting the hypothesis that 5′ UTR can act as a cellular Internal Ribosome Entry Site ( IRES) to modulate p16 INK 4a translation. [ABSTRACT FROM AUTHOR]

Published
2016
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37. Revisiting Li-Fraumeni Syndrome From TP53 Mutation Carriers.

Author

Bougeard, Gaëlle, Renaux-Petel, Mariette, Flaman, Jean-Michel, Charbonnier, Camille, Fermey, Pierre, Belotti, Muriel, Gauthier-Villars, Marion, Stoppa-Lyonnet, Dominique, Consolino, Emilie, Brugières, Laurence, Caron, Olivier, Benusiglio, Patrick R., Bressac-de Paillerets, Brigitte, Bonadona, Valérie, Bonaïti-Pellié, Catherine, Tinat, Julie, Baert-Desurmont, Stéphanie, and Frebourg, Thierry

Published
2015
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38. Multiple skin hamartomata: a possible novel clinical presentation of SUFU neoplasia syndrome.

Author

Mann, Kirsty, Magee, Jill, Guillaud-Bataille, Marine, Blondel, Christophe, Bressac-de Paillerets, Brigitte, Yeatman, Josie, and Winship, Ingrid

Abstract

Medulloblastoma tumours may arise sporadically or as part of an inherited syndrome. A subset of children with medulloblastoma carry germline and somatic mutations in the SUFU tumour suppressor gene located at 10q24. We report a 55 year old woman referred for investigation on the basis of skin lesions and a family history of two children from different unions with medulloblastoma. Examination of our patient revealed facial papules (classified as benign folliculosebaceous hamartomatous lesions) and dysmorphology (macrocephaly, hypertelorism and prognathism). She reported her father and her son share the same dermatological features; photographs of the son display hypertelorism. Sequencing in our patient revealed a splice-site mutation in intron 6 of SUFU (c. 756+1G>A), predicted to lead to skipping of exon 6. We suggest that the emerging phenotype in SUFU associated with familial medulloblastoma may include hamartomatous skin lesions. Consideration of these features, along with macrocephaly will alert clinicians to the likely genetic basis of the syndrome, affording the opportunity for genetic counselling, prenatal or pre-implantation genetic diagnosis in at-risk families. [ABSTRACT FROM AUTHOR]

Published
2015
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39. Functional characterization of a multi-cancer risk locus on chr5p15.33 reveals regulation of TERT by ZNF148

Author

Fang, Jun, Jia, Jinping, Makowski, Matthew, Xu, Mai, Wang, Zhaoming, Zhang, Tongwu, Hoskins, Jason W., Choi, Jiyeon, Han, Younghun, Zhang, Mingfeng, Thomas, Janelle, Kovacs, Michael, Collins, Irene, Dzyadyk, Marta, Thompson, Abbey, O'Neill, Maura, Das, Sudipto, Lan, Qi, Koster, Roelof, Canzian, Federico, Kooperberg, Charles, Arslan, Alan A, Bracci, Paige M, Buring, Julie, Duell, Eric J, Gallinger, Steven, Jacobs, Eric J, Kamineni, Aruna, Van Den Eeden, Stephen, Klein, Alison P, Kolonel, Laurence N, Li, Donghui, Olson, Sara H, Risch, Harvey A, Sesso, Howard D, Visvanathan, Kala, Zheng, Wei, Albanes, Demetrius, Austin, Melissa A, Boutron-Ruault, Marie-Christine, Bueno-de-Mesquita, H Bas, Cotterchio, Michelle, Gaziano, J Michael, Giovannucci, Edward L, Goggins, Michael, Gross, Myron, Hassan, Manal, Helzlsouer, Kathy J, Holly, Elizabeth A, Hunter, David J, Jenab, Mazda, Kaaks, Rudolf, Key, Timothy J, Khaw, Kay-Tee, Krogh, Vittorio, Kurtz, Robert C, LaCroix, Andrea, Le Marchand, Loic, Mannisto, Satu, Patel, Alpa V, Peeters, Petra H M, Riboli, Elio, Shu, Xiao-Ou, Sund, Malin, Thornquist, Mark, Tjønneland, Anne, Tobias, Geoffrey S, Trichopoulos, Dimitrios, Wactawski-Wende, Jean, Yu, Herbert, Yu, Kai, Zeleniuch-Jacquotte, Anne, Hoover, Robert, Hartge, Patricia, Fuchs, Charles, Chanock, Stephen J, Stevens, Victoria, Albanes, Demetrios, Caporaso, Neil E, Brennan, Paul, McKay, James, Wu, Xifeng, Hung, Rayjean J, McLaughlin, John R, Bickeboller, Heike, Risch, Angela, Wichmann, Erich, Houlston, Richard, Mann, Graham, Hopper, John, Aitken, Joanne, Armstrong, Bruce, Giles, Graham, Holland, Elizabeth, Kefford, Richard, Cust, Anne, Jenkins, Mark, Schmid, Helen, Puig, Susana, Aguilera, Paula, Badenas, Celia, Barreiro, Alicia, Carrera, Cristina, Gabriel, Daniel, Xavier, Pol Gimenez, Iglesias-Garcia, Pablo, Malvehy, Josep, Mila, Montse, Pigem, Ramon, Potrony, Miriam, Batille, Joan-AntonPuig, Marti, Gemma Tell, Hayward, Nick, Martin, Nicholas, Montgomery, Grant, Duffy, David, Whiteman, David, Gregor, Stuart Mac, Calista, Donato, Landi, Giorgi, Minghetti, Paola, Arcangeli, Fabio, Bertazzi, Pier Alberto, Ghiorzo, Paola, Scarra, Giovanna Bianchi, Pastorino, Lorenze, Bruno, William, Andreotti, Virginia, Queirolo, Paola, Spagnolo, Francesco, Mackie, Rona, Lang, Julie, Gruis, Nelleke, van Nieuwpoort, Frans A, Out, Coby, Bergman, Wilma, Kukutsch, Nicole, Bavinck, Jan Nico Bouwes, Bakker, Bert, van der Stoep, Nienke, ter Huurne, Jeanet, van der Rhee, Han, Bekkenk, Marcel, Snels, Dyon, van Praag, Marinus, Brochez, Lieve, Gerritsen, Rianne, Crijns, Marianne, Vasen, Hans, Janssen, Bart, Ingvar, Christian, Olsson, Hakan, Jonsson, Goran, Borg, Ake, Harbst, Katja, Nielsen, Kari, Zander, Anita Schmidt, Molvern, Anders, Helsing, Per, Andresen, Per Arne, Rootwelt, Helge, Akslen, Lars A, Bressac-de Paillerets, Brigitte, Demenais, Florence, Avril, Marie-Francoise, Chaudru, Valerie, Jeannin, Patricia, Lesueur, Fabienne, Maubec, Eve, Mohamdi, Hamida, Bossard, Myriam, Vaysse, Amaury, Boitier, Francoise, Caron, Oliver, Caux, Frederic, Dalle, Stephane, Dereure, Oliviier, Leroux, Dominique, Martin, Ludovic, Mateus, Christine, Robert, Caroline, Stoppa-Lyonnet, Dominique, Thomas, Luc, Wierzbicka, Eva, Elder, David, Ming, Michael, Mitra, Nandita, Debniak, Tadeusz, Lubinski, Jan, Hocevar, Marko, Novakovic, Srdjan, Peric, Barbara, Skerl, Petra, Hansson, Johan, Hoiom, Veronica, Freidman, Eitan, Azizi, Esther, Baron-Epel, Orna, Scope, Alon, Pavlotsky, Felix, Cohen-Manheim, Irit, Laitman, Yael, Harland, Mark, Randerson-Moor, Juliette, Laye, Jon, Davies, John, Nsengimana, Jeremie, O'Shea, Sally, Chan, May, Gascoyne, Jo, Tucker, Margaret A, Goldstein, Alisa M, Yang, Xiaohong R, Stolzenberg-Solomon, Rachael S., Kraft, Peter, Wolpin, Brian M., Jansen, Pascal W. T. C., Olson, Sara, McGlynn, Katherine A., Kanetsky, Peter A., Chatterjee, Nilanjan, Barrett, Jennifer H., Dunning, Alison M., Taylor, John C., Newton-Bishop, Julia A., Bishop, D. Timothy, Andresson, Thorkell, Petersen, Gloria M., Amos, Christopher I., Iles, Mark M., Nathanson, Katherine L., Landi, Maria Teresa, Vermeulen, Michiel, Brown, Kevin M., and Amundadottir, Laufey T.

Abstract

Genome wide association studies (GWAS) have mapped multiple independent cancer susceptibility loci to chr5p15.33. Here, we show that fine-mapping of pancreatic and testicular cancer GWAS within one of these loci (Region 2 in CLPTM1L) focuses the signal to nine highly correlated SNPs. Of these, rs36115365-C associated with increased pancreatic and testicular but decreased lung cancer and melanoma risk, and exhibited preferred protein-binding and enhanced regulatory activity. Transcriptional gene silencing of this regulatory element repressed TERT expression in an allele-specific manner. Proteomic analysis identifies allele-preferred binding of Zinc finger protein 148 (ZNF148) to rs36115365-C, further supported by binding of purified recombinant ZNF148. Knockdown of ZNF148 results in reduced TERT expression, telomerase activity and telomere length. Our results indicate that the association with chr5p15.33-Region 2 may be explained by rs36115365, a variant influencing TERT expression via ZNF148 in a manner consistent with elevated TERT in carriers of the C allele.

Published
2017
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40. Rare missense variants in POT1 predispose to familial cutaneous malignant melanoma.

Author

Shi, Jianxin, Yang, Xiaohong R, Ballew, Bari, Rotunno, Melissa, Calista, Donato, Fargnoli, Maria Concetta, Ghiorzo, Paola, Bressac-de Paillerets, Brigitte, Nagore, Eduardo, Avril, Marie Francoise, Caporaso, Neil E, McMaster, Mary L, Cullen, Michael, Wang, Zhaoming, Zhang, Xijun, Bruno, William, Pastorino, Lorenza, Queirolo, Paola, Banuls-Roca, Jose, and Garcia-Casado, Zaida

Subjects
MELANOMA, TELOMERES, CHROMOSOMES, NEUROENDOCRINE tumors, GENETIC mutation, ROMAGNA (Italy)
Abstract

Although CDKN2A is the most frequent high-risk melanoma susceptibility gene, the underlying genetic factors for most melanoma-prone families remain unknown. Using whole-exome sequencing, we identified a rare variant that arose as a founder mutation in the telomere shelterin gene POT1 (chromosome 7, g.124493086C>T; p.Ser270Asn) in five unrelated melanoma-prone families from Romagna, Italy. Carriers of this variant had increased telomere lengths and numbers of fragile telomeres, suggesting that this variant perturbs telomere maintenance. Two additional rare POT1 variants were identified in all cases sequenced in two separate Italian families, one variant per family, yielding a frequency for POT1 variants comparable to that for CDKN2A mutations in this population. These variants were not found in public databases or in 2,038 genotyped Italian controls. We also identified two rare recurrent POT1 variants in US and French familial melanoma cases. Our findings suggest that POT1 is a major susceptibility gene for familial melanoma in several populations. [ABSTRACT FROM AUTHOR]

Published
2014
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41. Diversity of the clinical presentation of the MMR gene biallelic mutations.

Author

Bougeard, Gaëlle, Olivier-Faivre, Laurence, Baert-Desurmont, Stéphanie, Tinat, Julie, Martin, Cosette, Bouvignies, Emilie, Vasseur, Stéphanie, Huet, Frédéric, Couillault, Gérard, Vabres, Pierre, Le Pessot, Florence, Chapusot, Caroline, Malka, David, Bressac-de Paillerets, Brigitte, Tosi, Mario, and Frebourg, Thierry

Abstract

Constitutional mismatch repair-deficiency, due to biallelic mutations of MMR genes, results in a tumour spectrum characterized by leukaemias, lymphomas, brain tumours and adenocarcinomas of the gastro-intestinal tract, occurring mostly in childhood. We report here two families illustrating the phenotypic diversity associated with biallelic MMR mutations. In the first family, two siblings developed six malignancies including glioblastoma, lymphoblastic T cell lymphoma, rectal and small bowel adenocarcinoma with onset as early as 6 years of age. We showed that this dramatic clinical presentation was due to the presence of two complex genomic PMS2 deletions in each patient predicted to result into complete PMS2 inactivation. In the second family, the index case presented with an early form of Lynch syndrome with colorectal adenocarcinomas at ages 17 and 20 years, and urinary tract tumours at the age of 25 years. We identified in this patient two MSH6 mutations corresponding to a frameshift deletion and an in frame deletion. The latter was not predicted to result into complete inactivation of MSH6. These reports show that the clinical expression of biallelic MMR mutations depends on the biological impact of the second MMR mutation and that, in clinical practice, the presence of a second MMR mutation located in trans should also be considered in patients suspected to present a Lynch syndrome with an unusual early-onset of tumours. [ABSTRACT FROM AUTHOR]

Published
2014
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42. Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast–ovarian cancer susceptibility locus

Author

Lawrenson, Kate, Kar, Siddhartha, McCue, Karen, Kuchenbaeker, Karoline, Michailidou, Kyriaki, Tyrer, Jonathan, Beesley, Jonathan, Ramus, Susan J., Li, Qiyuan, Delgado, Melissa K., Lee, Janet M., Aittomäki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Arun, Banu K., Arver, Brita, Bandera, Elisa V., Barile, Monica, Barkardottir, Rosa B., Barrowdale, Daniel, Beckmann, Matthias W., Benitez, Javier, Berchuck, Andrew, Bisogna, Maria, Bjorge, Line, Blomqvist, Carl, Blot, William, Bogdanova, Natalia, Bojesen, Anders, Bojesen, Stig E., Bolla, Manjeet K., Bonanni, Bernardo, Børresen-Dale, Anne-Lise, Brauch, Hiltrud, Brennan, Paul, Brenner, Hermann, Bruinsma, Fiona, Brunet, Joan, Buhari, Shaik Ahmad, Burwinkel, Barbara, Butzow, Ralf, Buys, Saundra S., Cai, Qiuyin, Caldes, Trinidad, Campbell, Ian, Canniotto, Rikki, Chang-Claude, Jenny, Chiquette, Jocelyne, Choi, Ji-Yeob, Claes, Kathleen B. M., Collonge-Rame, Marie- Agnès, Damette, Alexandre, Barouk-Simonet, Emmanuelle, Bonnet, Françoise, Bubien, Virginie, Sevenet, Nicolas, Longy, Michel, Berthet, Pascaline, Vaur, Dominique, Castera, Laurent, Ferrer, Sandra Fert, Bignon, Yves-Jean, Uhrhammer, Nancy, Coron, Fanny, Faivre, Laurence, Baurand, Amandine, Jacquot, Caroline, Bertolone, Geoffrey, Lizard, Sarab, Leroux, Dominique, Dreyfus, Hélène, Rebischung, Christine, Peysselon, Magalie, Peyrat, Jean-Philippe, Fournier, Joëlle, Révillion, Françoise, Adenis, Claude, Vénat-Bouvet, Laurence, Léone, Mélanie, Boutry-Kryza, Nadia, Calender, Alain, Giraud, Sophie, Verny-Pierre, Carole, Lasset, Christine, Bonadona, Valérie, Barjhoux, Laure, Sobol, Hagay, Bourdon, Violaine, Noguchi, Tetsuro, Remenieras, Audrey, Coupier, Isabelle, Pujol, Pascal, Sokolowska, Johanna, Bronner, Myriam, Delnatte, Capucine, Bézieau, Stéphane, Mari, Véronique, Gauthier-Villars, Marion, Buecher, Bruno, Rouleau, Etienne, Golmard, Lisa, Moncoutier, Virginie, Belotti, Muriel, de Pauw, Antoine, Elan, Camille, Fourme, Emmanuelle, Birot, Anne-Marie, Saule, Claire, Laurent, Maïté, Houdayer, Claude, Lesueur, Fabienne, Mebirouk, Noura, Coulet, Florence, Colas, Chrystelle, Soubrier, Florent, Warcoin, Mathilde, Prieur, Fabienne, Lebrun, Marine, Kientz, Caroline, Muller, Danièle, Fricker, Jean-Pierre, Toulas, Christine, Guimbaud, Rosine, Gladieff, Laurence, Feillel, Viviane, Mortemousque, Isabelle, Bressac-de-Paillerets, Brigitte, Caron, Olivier, Guillaud-Bataille, Marine, Cook, Linda S., Cox, Angela, Cramer, Daniel W., Cross, Simon S., Cybulski, Cezary, Czene, Kamila, Daly, Mary B., Damiola, Francesca, Dansonka-Mieszkowska, Agnieszka, Darabi, Hatef, Dennis, Joe, Devilee, Peter, Diez, Orland, Doherty, Jennifer A., Domchek, Susan M., Dorfling, Cecilia M., Dörk, Thilo, Dumont, Martine, Ehrencrona, Hans, Ejlertsen, Bent, Ellis, Steve, Gregory, Helen, Miedzybrodzka, Zosia, Morrison, Patrick J., Donaldson, Alan, Rogers, Mark T., Kennedy, M. John, Porteous, Mary E., Brady, Angela, Barwell, Julian, Foo, Claire, Lalloo, Fiona, Side, Lucy E., Eason, Jacqueline, Henderson, Alex, Walker, Lisa, Cook, Jackie, Snape, Katie, Murray, Alex, McCann, Emma, Engel, Christoph, Lee, Eunjung, Evans, D. Gareth, Fasching, Peter A., Feliubadalo, Lidia, Figueroa, Jonine, Flesch-Janys, Dieter, Fletcher, Olivia, Flyger, Henrik, Foretova, Lenka, Fostira, Florentia, Foulkes, William D., Fridley, Brooke L., Friedman, Eitan, Frost, Debra, Gambino, Gaetana, Ganz, Patricia A., Garber, Judy, García-Closas, Montserrat, Gentry-Maharaj, Aleksandra, Ghoussaini, Maya, Giles, Graham G., Glasspool, Rosalind, Godwin, Andrew K., Goldberg, Mark S., Goldgar, David E., González-Neira, Anna, Goode, Ellen L., Goodman, Marc T., Greene, Mark H., Gronwald, Jacek, Guénel, Pascal, Haiman, Christopher A., Hall, Per, Hallberg, Emily, Hamann, Ute, Hansen, Thomas V. O., Harrington, Patricia A., Hartman, Mikael, Hassan, Norhashimah, Healey, Sue, Rookus, M. A., van Leeuwen, F. E., van der Kolk, L. E., Schmidt, M. K., Russell, N. S., de Lange, J. L., Wijnands, R., Collée, J. M., Hooning, M. J., Seynaeve, C., van Deurzen, C. H. M., Obdeijn, I. M., van Asperen, C. J., Tollenaar, R. A. E. M., van Cronenburg, T. C. T. E. F., Kets, C. M., Ausems, M. G. E. M., van der Pol, C. C., van Os, T. A. M., Waisfisz, Q., Meijers-Heijboer, H. E. J., Gómez-Garcia, E. B., Oosterwijk, J. C., Mourits, M. J., de Bock, G. H., Vasen, H. F., Siesling, S., Verloop, J., Overbeek, L. I. H., Heitz, Florian, Herzog, Josef, Høgdall, Estrid, Høgdall, Claus K., Hogervorst, Frans B. L., Hollestelle, Antoinette, Hopper, John L., Hulick, Peter J., Huzarski, Tomasz, Imyanitov, Evgeny N., Fox, Stephen, Kirk, Judy, Lindeman, Geoff, Price, Melanie, Bowtell, David, deFazio, Anna, Webb, Penny, Isaacs, Claudine, Ito, Hidemi, Jakubowska, Anna, Janavicius, Ramunas, Jensen, Allan, John, Esther M., Johnson, Nichola, Kabisch, Maria, Kang, Daehee, Kapuscinski, Miroslav, Karlan, Beth Y., Khan, Sofia, Kiemeney, Lambertus A., Kjaer, Susanne Kruger, Knight, Julia A., Konstantopoulou, Irene, Kosma, Veli-Matti, Kristensen, Vessela, Kupryjanczyk, Jolanta, Kwong, Ava, de la Hoya, Miguel, Laitman, Yael, Lambrechts, Diether, Le, Nhu, De Leeneer, Kim, Lester, Jenny, Levine, Douglas A., Li, Jingmei, Lindblom, Annika, Long, Jirong, Lophatananon, Artitaya, Loud, Jennifer T., Lu, Karen, Lubinski, Jan, Mannermaa, Arto, Manoukian, Siranoush, Le Marchand, Loic, Margolin, Sara, Marme, Frederik, Massuger, Leon F. A. G., Matsuo, Keitaro, Mazoyer, Sylvie, McGuffog, Lesley, McLean, Catriona, McNeish, Iain, Meindl, Alfons, Menon, Usha, Mensenkamp, Arjen R., Milne, Roger L., Montagna, Marco, Moysich, Kirsten B., Muir, Kenneth, Mulligan, Anna Marie, Nathanson, Katherine L., Ness, Roberta B., Neuhausen, Susan L., Nevanlinna, Heli, Nord, Silje, Nussbaum, Robert L., Odunsi, Kunle, Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo I., Olson, Janet E., Olswold, Curtis, O'Malley, David, Orlow, Irene, Orr, Nick, Osorio, Ana, Park, Sue Kyung, Pearce, Celeste L., Pejovic, Tanja, Peterlongo, Paolo, Pfeiler, Georg, Phelan, Catherine M., Poole, Elizabeth M., Pylkäs, Katri, Radice, Paolo, Rantala, Johanna, Rashid, Muhammad Usman, Rennert, Gad, Rhenius, Valerie, Rhiem, Kerstin, Risch, Harvey A., Rodriguez, Gus, Rossing, Mary Anne, Rudolph, Anja, Salvesen, Helga B., Sangrajrang, Suleeporn, Sawyer, Elinor J., Schildkraut, Joellen M., Schmidt, Marjanka K., Schmutzler, Rita K., Sellers, Thomas A., Seynaeve, Caroline, Shah, Mitul, Shen, Chen-Yang, Shu, Xiao-Ou, Sieh, Weiva, Singer, Christian F., Sinilnikova, Olga M., Slager, Susan, Song, Honglin, Soucy, Penny, Southey, Melissa C., Stenmark-Askmalm, Marie, Stoppa-Lyonnet, Dominique, Sutter, Christian, Swerdlow, Anthony, Tchatchou, Sandrine, Teixeira, Manuel R., Teo, Soo H., Terry, Kathryn L., Terry, Mary Beth, Thomassen, Mads, Tibiletti, Maria Grazia, Tihomirova, Laima, Tognazzo, Silvia, Toland, Amanda Ewart, Tomlinson, Ian, Torres, Diana, Truong, Thérèse, Tseng, Chiu-chen, Tung, Nadine, Tworoger, Shelley S., Vachon, Celine, van den Ouweland, Ans M. W., van Doorn, Helena C., van Rensburg, Elizabeth J., Van't Veer, Laura J., Vanderstichele, Adriaan, Vergote, Ignace, Vijai, Joseph, Wang, Qin, Wang-Gohrke, Shan, Weitzel, Jeffrey N., Wentzensen, Nicolas, Whittemore, Alice S., Wildiers, Hans, Winqvist, Robert, Wu, Anna H., Yannoukakos, Drakoulis, Yoon, Sook-Yee, Yu, Jyh-Cherng, Zheng, Wei, Zheng, Ying, Khanna, Kum Kum, Simard, Jacques, Monteiro, Alvaro N., French, Juliet D., Couch, Fergus J., Freedman, Matthew L., Easton, Douglas F., Dunning, Alison M., Pharoah, Paul D., Edwards, Stacey L., Chenevix-Trench, Georgia, Antoniou, Antonis C., and Gayther, Simon A.

Abstract

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10−20), ER-negative BC (P=1.1 × 10−13), BRCA1-associated BC (P=7.7 × 10−16) and triple negative BC (P-diff=2 × 10−5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10−3) and ABHD8 (P<2 × 10−3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.

Published
2016
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44. Genome-wide association study identifies three new melanoma susceptibility loci.

Author

Barrett, Jennifer H, Iles, Mark M, Harland, Mark, Taylor, John C, Aitken, Joanne F, Andresen, Per Arne, Akslen, Lars A, Armstrong, Bruce K, Avril, Marie-Francoise, Azizi, Esther, Bakker, Bert, Bergman, Wilma, Bianchi-Scarrà, Giovanna, Bressac-de Paillerets, Brigitte, Calista, Donato, Cannon-Albright, Lisa A, Corda, Eve, Cust, Anne E, D?bniak, Tadeusz, and Duffy, David

Subjects
MELANOMA diagnosis, DISEASE susceptibility, GENETIC polymorphisms, GENOTYPE-environment interaction, PHENOTYPES, EUROPEANS, HEALTH
Abstract

We report a genome-wide association study for melanoma that was conducted by the GenoMEL Consortium. Our discovery phase included 2,981 individuals with melanoma and 1,982 study-specific control individuals of European ancestry, as well as an additional 6,426 control subjects from French or British populations, all of whom were genotyped for 317,000 or 610,000 single-nucleotide polymorphisms (SNPs). Our analysis replicated previously known melanoma susceptibility loci. Seven new regions with at least one SNP with P < 10?5 and further local imputed or genotyped support were selected for replication using two other genome-wide studies (from Australia and Texas, USA). Additional replication came from case-control series from the UK and The Netherlands. Variants at three of the seven loci replicated at P < 10?3: an SNP in ATM (rs1801516, overall P = 3.4 × 10?9), an SNP in MX2 (rs45430, P = 2.9 × 10?9) and an SNP adjacent to CASP8 (rs13016963, P = 8.6 × 10?10). A fourth locus near CCND1 remains of potential interest, showing suggestive but inconclusive evidence of replication (rs1485993, overall P = 4.6 × 10?7 under a fixed-effects model and P = 1.2 × 10?3 under a random-effects model). These newly associated variants showed no association with nevus or pigmentation phenotypes in a large British case-control series. [ABSTRACT FROM AUTHOR]

Published
2011
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46. Novel diagnostic tool for prediction of variant spliceogenicity derived from a set of 395 combined in silico/in vitro studies: an international collaborative effort.

Author

Leman, Raphaël, Gaildrat, Pascaline, Le Gac, Gérald, Ka, Chandran, Fichou, Yann, Audrezet, Marie-Pierre, Caux-Moncoutier, Virginie, Caputo, Sandrine M, Boutry-Kryza, Nadia, Léone, Mélanie, Mazoyer, Sylvie, Bonnet-Dorion, Françoise, Sevenet, Nicolas, Guillaud-Bataille, Marine, Rouleau, Etienne, Bressac-de Paillerets, Brigitte, Wappenschmidt, Barbara, Rossing, Maria, Muller, Danielle, and Bourdon, Violaine

Published
2020
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47. Influence of Genes, Nevi, and Sun Sensitivity on Melanoma Risk in a Family Sample Unselected by Family History and in Melanoma-Prone Families.

Author

Chaudru, Valérie, Chompret, Agnès, Bressac-de Paillerets, Brigitte, Spatz, Alain, Avril, Marie-Françoise, and Demenais, Florence

Subjects
MELANOMA, CANCER risk factors, HEREDITY, GENETICS, FAMILIES, CANCER research
Abstract

Background: Few family studies have investigated the effects of genetic, environmental, and host factors on melanoma risk, and most have been restricted to high-risk families. We assessed the role of these factors on melanoma risk in two types of families: families ascertained through melanoma probands but unselected by family history and melanoma-prone families. Methods: Data on pigmentary traits, nevus phenotypes, exposure to sun, and reactions to sunlight were collected from 295 families unselected by family history and 53 melanoma-prone families. We modeled melanoma risk using a logistic regressive model incorporating the effect of a melanoma-predisposing gene, familial dependence, and potential risk factors (e.g., pigmentary traits, nevus phenotypes, history of sun exposure, skin reactions to sunlight). Maximum-likelihood estimates of the parameters of the regressive model were used to compute odds ratios associated with each risk factor and age-specific melanoma risk depending on the genotype at the melanoma-predisposing gene and the effects of risk factors. Ali statistical tests were two-sided. Results: In the families unselected by family history, there was statistically significant evidence (P<.001) for a dominant gene, with melanoma risk reaching 0.49 and 0.67 by age 80 years in male and female gene carriers, respectively. Melanoma risk was statistically significantly influenced by total nevi (odds ratio of hazard function [OR] = 5.81, 95% confidence interval [CI] = 3.47 to 8.99), sun exposure (OR = 5.37, 95% CI = 4.44 to 6.36), and sunburn interacting with the gene (OR = 26.31, 95% CI = 7.56 to 99.22 in gene carriers and OR = 1.67, 95 % CI = 1.36 to 2.03 in noncarriers). Twenty of the 53 melanoma-prone families had co-segregating mutations in CDKN2A, a gene known to be associated with melanoma. In these 53 families, three risk factors in addition to CDKN2A mutations increased melanoma risk: dysplastic nevi (OR = 2.32, 95% CI = 2.08 to 2.58), total nevi (OR = 1.99, 95% CI = 1.61 to 2.20) and sunburn (OR = 5.16, 95% CI = 4.82 to 5.52). Conclusions: Together, a melanoma-predisposing gene (identified as being CDKN2A in melanoma-prone families), number of nevi and/or dysplastic nevi, and sun-related covariates influence melanoma risk in both families unselected by family history and melanoma-prone families. [J Natl Cancer Inst 2004;96: 785-95] [ABSTRACT FROM AUTHOR]

Published
2004
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48. Impact of gene patents on the cost-effective delivery of care: the case of BRCA1 genetic testing.

Author

Sevilla, Christine, Julian-Reynier, Claire, Eisinger, François, Stoppa-Lyonnet, Dominique, Bressac-de Paillerets, Brigitte, Sobol, Hagay, and Moatti, Jean-Paul

Abstract

Background: In 1994/95, two genes, BRCA1/2, associated with a predisposition to breast or ovarian cancer were identified. Genetic testing of deleterious BRCA1/2 mutations consequently can be proposed to individuals with a family history of breast or ovarian cancer to identify who is at risk. The granting of U.S. patents on BRCA1/2 to a privately owned company has led to the monopoly use of a unique technique (Direct Sequencing of the gene, DS) for BRCA1/2 testing in this country. Alternative strategies using prescreening techniques, however, have been experienced worldwide.Methods: On the basis of data collected at three laboratories of French public hospitals, we carried out a cost-effectiveness study comparing DS to 19 alternative strategies with the number of deleterious BRCA1 mutations detected as the outcome.Results: Results show that the DS strategy presents the highest average cost per mutation detected (9,882.5 Euro) and that there exist strategies using prescreening techniques that can reach similar effectiveness while reducing total costs. Moreover, other strategies can obtain a four- to sevenfold reduction in the average cost per mutation detected as soon as some rates of false negatives (2% to 13%) are deemed to be acceptable.Conclusions: Results suggest that gene patents with a very broad scope, covering all potential medical applications, may prevent health care systems from identifying and adopting the most efficient genetic testing strategies due to the monopoly granted for the exploitation of the gene. Policy implications for regulatory authorities, in the current context of the extension of BRCA1/2 patents in other countries, are discussed. [ABSTRACT FROM AUTHOR]

Published
2003
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49. Geographical variation in the penetrance of CDKN2A mutations for melanoma.

Author

Bishop, D. Timothy, Demenais, Florence, Goldstein, Alisa M., Bergman, Wilma, Bishop, Julia Newton, Bressac-de Paillerets, Brigitte, Chompret, Agnès, Ghiorzo, Paola, Gruis, Nelleke, Hansson, Johan, Harland, Mark, Hayward, Nicholas, Holland, Elizabeth A., Mann, Graham J., Mantelli, Michela, Nancarrow, Derek, Platz, Anton, Tucker, Margaret A., Chompret, Agnès, and Melanoma Genetics Consortium

Subjects
MELANOMA, GENETIC mutation, CHROMOSOMES, COMPARATIVE studies, DISEASE susceptibility, FAMILIES, GENETICS, RESEARCH methodology, MEDICAL cooperation, ONCOGENES, POPULATION geography, PROTEINS, RESEARCH, EVALUATION research
Abstract

Background: Germline mutations in the CDKN2A gene, which encodes two proteins (p16INK4A and p14ARF), are the most common cause of inherited susceptibility to melanoma. We examined the penetrance of such mutations using data from eight groups from Europe, Australia and the United States that are part of The Melanoma Genetics Consortium.Methods: We analyzed 80 families with documented CDKN2A mutations and multiple cases of cutaneous melanoma. We modeled penetrance for melanoma using a logistic regression model incorporating survival analysis. Hypothesis testing was based on likelihood ratio tests. Covariates included gender, alterations in p14ARF protein, and population melanoma incidence rates. All statistical tests were two-sided.Results: The 80 analyzed families contained 402 melanoma patients, 320 of whom were tested for mutations and 291 were mutation carriers. We also tested 713 unaffected family members for mutations and 194 were carriers. Overall, CDKN2A mutation penetrance was estimated to be 0.30 (95% confidence interval (CI) = 0.12 to 0.62) by age 50 years and 0.67 (95% CI = 0.31 to 0.96) by age 80 years. Penetrance was not statistically significantly modified by gender or by whether the CDKN2A mutation altered p14ARF protein. However, there was a statistically significant effect of residing in a location with a high population incidence rate of melanoma (P =.003). By age 50 years CDKN2A mutation penetrance reached 0.13 in Europe, 0.50 in the United States, and 0.32 in Australia; by age 80 years it was 0.58 in Europe, 0.76 in the United States, and 0.91 in Australia.Conclusions: This study, which gives the most informed estimates of CDKN2A mutation penetrance available, indicates that the penetrance varies with melanoma population incidence rates. Thus, the same factors that affect population incidence of melanoma may also mediate CDKN2A penetrance. [ABSTRACT FROM AUTHOR]

Published
2002
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50. Genetic and environmental factors in cutaneous malignant melanoma

Author

Bressac-de-Paillerets, Brigitte, Avril, Marie-Françoise, Chompret, Agnès, and Demenais, Florence

Subjects
*MELANOMA, *FAMILIAL diseases
Abstract

Cutaneous malignant melanoma (CMM) is an interesting example of multifactorial disease, where both genetic and environmental factors are involved and interact. Major risk factors include a personal and familial history of melanoma, cutaneous and pigmentary characteristics, sun exposure and reactions to sun exposure. Phenotypic risk factors are likely to be genetically determined. Two high-risk melanoma susceptibility genes—CDKN2A and CDK4—have been identified to date, with a third gene p14ARF also being suspected of playing a role. Other high-risk genes are anticipated by the existence of 9p21-unlinked families. A low-risk melanoma-susceptibility gene—MC1R—has also been identified. Current studies aim to identify other susceptibility genes as well as to determine the respective contributions and interactions of the various genetic and environmental factors of CMM and associated phenotypes. [Copyright &y& Elsevier]

Published
2002
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