Search

Your search keyword '"Mendoza-Fandiño, Gustavo"' showing total 20 results
Start Over Author "Mendoza-Fandiño, Gustavo"
20 results on '"Mendoza-Fandiño, Gustavo"'

2. Functional analysis and fine mapping of the 9p22.2 ovarian cancer susceptibility locus

Author

Buckley, Melissa A, Woods, Nicholas T, Tyrer, Jonathan P, Mendoza-Fandiño, Gustavo, Lawrenson, Kate, Hazelett, Dennis J, Najafabadi, Hamed S, Gjyshi, Anxhela, Carvalho, Renato S, Lyra, Paulo C, Coetzee, Simon G, Shen, Howard C, Yang, Ally W, Earp, Madalene A, Yoder, Sean J, Risch, Harvey, Chenevix-Trench, Georgia, Ramus, Susan J, Phelan, Catherine M, Coetzee, Gerhard A, Noushmehr, Houtan, Hughes, Timothy R, Sellers, Thomas A, Goode, Ellen L, Pharoah, Paul D, Gayther, Simon A, and Monteiro, Alvaro NA

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Genetics, Human Genome, Ovarian Cancer, Women's Health, Rare Diseases, Prevention, Biotechnology, Cancer, 2.1 Biological and endogenous factors, Base Sequence, Carcinoma, Ovarian Epithelial, Cell Cycle Proteins, Cell Line, Tumor, Chromosome Mapping, Chromosomes, Human, Pair 9, Cystadenocarcinoma, Serous, DNA, Neoplasm, DNA-Binding Proteins, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, HEK293 Cells, Humans, Linkage Disequilibrium, Ovarian Neoplasms, Polymorphism, Single Nucleotide, Ovarian Cancer Association Consortium, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

Genome-wide association studies have identified 40 ovarian cancer risk loci. However, the mechanisms underlying these associations remain elusive. In this study, we conducted a two-pronged approach to identify candidate causal SNPs and assess underlying biological mechanisms at chromosome 9p22.2, the first and most statistically significant associated locus for ovarian cancer susceptibility. Three transcriptional regulatory elements with allele-specific effects and a scaffold/matrix attachment region were characterized and, through physical DNA interactions, BNC2 was established as the most likely target gene. We determined the consensus binding sequence for BNC2 in vitro, verified its enrichment in BNC2 ChIP-seq regions, and validated a set of its downstream target genes. Fine-mapping by dense regional genotyping in over 15,000 ovarian cancer cases and 30,000 controls identified SNPs in the scaffold/matrix attachment region as among the most likely causal variants. This study reveals a comprehensive regulatory landscape at 9p22.2 and proposes a likely mechanism of susceptibility to ovarian cancer. SIGNIFICANCE: Mapping the 9p22.2 ovarian cancer risk locus identifies BNC2 as an ovarian cancer risk gene.See related commentary by Choi and Brown, p. 439.

Published
2019

3. Supplementary Table 5 from Functional Analysis and Fine Mapping of the 9p22.2 Ovarian Cancer Susceptibility Locus

Author

Buckley, Melissa A., primary, Woods, Nicholas T., primary, Tyrer, Jonathan P., primary, Mendoza-Fandiño, Gustavo, primary, Lawrenson, Kate, primary, Hazelett, Dennis J., primary, Najafabadi, Hamed S., primary, Gjyshi, Anxhela, primary, Carvalho, Renato S., primary, Lyra, Paulo C., primary, Coetzee, Simon G., primary, Shen, Howard C., primary, Yang, Ally W., primary, Earp, Madalene A., primary, Yoder, Sean J., primary, Risch, Harvey, primary, Chenevix-Trench, Georgia, primary, Ramus, Susan J., primary, Phelan, Catherine M., primary, Coetzee, Gerhard A., primary, Noushmehr, Houtan, primary, Hughes, Timothy R., primary, Sellers, Thomas A., primary, Goode, Ellen L., primary, Pharoah, Paul D., primary, Gayther, Simon A., primary, and Monteiro, Alvaro N.A., primary

Published
2023
Full Text
View/download PDF

4. Supplementary Figures 1-4 and extended methods from Functional Analysis and Fine Mapping of the 9p22.2 Ovarian Cancer Susceptibility Locus

Author

Buckley, Melissa A., primary, Woods, Nicholas T., primary, Tyrer, Jonathan P., primary, Mendoza-Fandiño, Gustavo, primary, Lawrenson, Kate, primary, Hazelett, Dennis J., primary, Najafabadi, Hamed S., primary, Gjyshi, Anxhela, primary, Carvalho, Renato S., primary, Lyra, Paulo C., primary, Coetzee, Simon G., primary, Shen, Howard C., primary, Yang, Ally W., primary, Earp, Madalene A., primary, Yoder, Sean J., primary, Risch, Harvey, primary, Chenevix-Trench, Georgia, primary, Ramus, Susan J., primary, Phelan, Catherine M., primary, Coetzee, Gerhard A., primary, Noushmehr, Houtan, primary, Hughes, Timothy R., primary, Sellers, Thomas A., primary, Goode, Ellen L., primary, Pharoah, Paul D., primary, Gayther, Simon A., primary, and Monteiro, Alvaro N.A., primary

Published
2023
Full Text
View/download PDF

5. Supplementary Table 3 from Functional Analysis and Fine Mapping of the 9p22.2 Ovarian Cancer Susceptibility Locus

Author

Buckley, Melissa A., primary, Woods, Nicholas T., primary, Tyrer, Jonathan P., primary, Mendoza-Fandiño, Gustavo, primary, Lawrenson, Kate, primary, Hazelett, Dennis J., primary, Najafabadi, Hamed S., primary, Gjyshi, Anxhela, primary, Carvalho, Renato S., primary, Lyra, Paulo C., primary, Coetzee, Simon G., primary, Shen, Howard C., primary, Yang, Ally W., primary, Earp, Madalene A., primary, Yoder, Sean J., primary, Risch, Harvey, primary, Chenevix-Trench, Georgia, primary, Ramus, Susan J., primary, Phelan, Catherine M., primary, Coetzee, Gerhard A., primary, Noushmehr, Houtan, primary, Hughes, Timothy R., primary, Sellers, Thomas A., primary, Goode, Ellen L., primary, Pharoah, Paul D., primary, Gayther, Simon A., primary, and Monteiro, Alvaro N.A., primary

Published
2023
Full Text
View/download PDF

6. Data from Functional Analysis and Fine Mapping of the 9p22.2 Ovarian Cancer Susceptibility Locus

Author

Buckley, Melissa A., primary, Woods, Nicholas T., primary, Tyrer, Jonathan P., primary, Mendoza-Fandiño, Gustavo, primary, Lawrenson, Kate, primary, Hazelett, Dennis J., primary, Najafabadi, Hamed S., primary, Gjyshi, Anxhela, primary, Carvalho, Renato S., primary, Lyra, Paulo C., primary, Coetzee, Simon G., primary, Shen, Howard C., primary, Yang, Ally W., primary, Earp, Madalene A., primary, Yoder, Sean J., primary, Risch, Harvey, primary, Chenevix-Trench, Georgia, primary, Ramus, Susan J., primary, Phelan, Catherine M., primary, Coetzee, Gerhard A., primary, Noushmehr, Houtan, primary, Hughes, Timothy R., primary, Sellers, Thomas A., primary, Goode, Ellen L., primary, Pharoah, Paul D., primary, Gayther, Simon A., primary, and Monteiro, Alvaro N.A., primary

Published
2023
Full Text
View/download PDF

7. Supplementary Table 1 from Functional Analysis and Fine Mapping of the 9p22.2 Ovarian Cancer Susceptibility Locus

Author

Buckley, Melissa A., primary, Woods, Nicholas T., primary, Tyrer, Jonathan P., primary, Mendoza-Fandiño, Gustavo, primary, Lawrenson, Kate, primary, Hazelett, Dennis J., primary, Najafabadi, Hamed S., primary, Gjyshi, Anxhela, primary, Carvalho, Renato S., primary, Lyra, Paulo C., primary, Coetzee, Simon G., primary, Shen, Howard C., primary, Yang, Ally W., primary, Earp, Madalene A., primary, Yoder, Sean J., primary, Risch, Harvey, primary, Chenevix-Trench, Georgia, primary, Ramus, Susan J., primary, Phelan, Catherine M., primary, Coetzee, Gerhard A., primary, Noushmehr, Houtan, primary, Hughes, Timothy R., primary, Sellers, Thomas A., primary, Goode, Ellen L., primary, Pharoah, Paul D., primary, Gayther, Simon A., primary, and Monteiro, Alvaro N.A., primary

Published
2023
Full Text
View/download PDF

8. Supplementary Table 2 from Functional Analysis and Fine Mapping of the 9p22.2 Ovarian Cancer Susceptibility Locus

Author

Buckley, Melissa A., primary, Woods, Nicholas T., primary, Tyrer, Jonathan P., primary, Mendoza-Fandiño, Gustavo, primary, Lawrenson, Kate, primary, Hazelett, Dennis J., primary, Najafabadi, Hamed S., primary, Gjyshi, Anxhela, primary, Carvalho, Renato S., primary, Lyra, Paulo C., primary, Coetzee, Simon G., primary, Shen, Howard C., primary, Yang, Ally W., primary, Earp, Madalene A., primary, Yoder, Sean J., primary, Risch, Harvey, primary, Chenevix-Trench, Georgia, primary, Ramus, Susan J., primary, Phelan, Catherine M., primary, Coetzee, Gerhard A., primary, Noushmehr, Houtan, primary, Hughes, Timothy R., primary, Sellers, Thomas A., primary, Goode, Ellen L., primary, Pharoah, Paul D., primary, Gayther, Simon A., primary, and Monteiro, Alvaro N.A., primary

Published
2023
Full Text
View/download PDF

9. Supplementary Table 4 from Functional Analysis and Fine Mapping of the 9p22.2 Ovarian Cancer Susceptibility Locus

Author

Buckley, Melissa A., primary, Woods, Nicholas T., primary, Tyrer, Jonathan P., primary, Mendoza-Fandiño, Gustavo, primary, Lawrenson, Kate, primary, Hazelett, Dennis J., primary, Najafabadi, Hamed S., primary, Gjyshi, Anxhela, primary, Carvalho, Renato S., primary, Lyra, Paulo C., primary, Coetzee, Simon G., primary, Shen, Howard C., primary, Yang, Ally W., primary, Earp, Madalene A., primary, Yoder, Sean J., primary, Risch, Harvey, primary, Chenevix-Trench, Georgia, primary, Ramus, Susan J., primary, Phelan, Catherine M., primary, Coetzee, Gerhard A., primary, Noushmehr, Houtan, primary, Hughes, Timothy R., primary, Sellers, Thomas A., primary, Goode, Ellen L., primary, Pharoah, Paul D., primary, Gayther, Simon A., primary, and Monteiro, Alvaro N.A., primary

Published
2023
Full Text
View/download PDF

10. Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer

Author

Phelan, Catherine M, Kuchenbaecker, Karoline B, Tyrer, Jonathan P, Kar, Siddhartha P, Lawrenson, Kate, Winham, Stacey J, Dennis, Joe, Pirie, Ailith, Riggan, Marjorie J, Chornokur, Ganna, Earp, Madalene A, Lyra, Jr, Paulo C, Lee, Janet M, Coetzee, Simon, Beesley, Jonathan, McGuffog, Lesley, Soucy, Penny, Dicks, Ed, Lee, Andrew, Barrowdale, Daniel, Lecarpentier, Julie, Leslie, Goska, Aalfs, Cora M, Aben, Katja K H, Adams, Marcia, Adlard, Julian, Andrulis, Irene L, Anton-Culver, Hoda, Antonenkova, Natalia, Aravantinos, Gerasimos, Arnold, Norbert, Arun, Banu K, Arver, Brita, Azzollini, Jacopo, Balmaña, Judith, Banerjee, Susana N, Barjhoux, Laure, Barkardottir, Rosa B, Bean, Yukie, Beckmann, Matthias W, Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Bernardini, Marcus Q, Birrer, Michael J, Bjorge, Line, Black, Amanda, Blankstein, Kenneth, Blok, Marinus J, Bodelon, Clara, Bogdanova, Natalia, Bojesen, Anders, Bonanni, Bernardo, Borg, Åke, Bradbury, Angela R, Brenton, James D, Brewer, Carole, Brinton, Louise, Broberg, Per, Brooks-Wilson, Angela, Bruinsma, Fiona, Brunet, Joan, Buecher, Bruno, Butzow, Ralf, Buys, Saundra S, Caldes, Trinidad, Caligo, Maria A, Campbell, Ian, Cannioto, Rikki, Carney, Michael E, Cescon, Terence, Chan, Salina B, Chang-Claude, Jenny, Chanock, Stephen, Chen, Xiao Qing, Chiew, Yoke-Eng, Chiquette, Jocelyne, Chung, Wendy K, Claes, Kathleen B M, Conner, Thomas, Cook, Linda S, Cook, Jackie, Cramer, Daniel W, Cunningham, Julie M, D'Aloisio, Aimee A, Daly, Mary B, Damiola, Francesca, Damirovna, Sakaeva Dina, Dansonka-Mieszkowska, Agnieszka, Dao, Fanny, Davidson, Rosemarie, DeFazio, Anna, Delnatte, Capucine, Doheny, Kimberly F, Diez, Orland, Ding, Yuan Chun, Doherty, Jennifer Anne, Domchek, Susan M, Dorfling, Cecilia M, Dörk, Thilo, Dossus, Laure, Duran, Mercedes, Dürst, Matthias, Dworniczak, Bernd, Eccles, Diana, Edwards, Todd, Eeles, Ros, Eilber, Ursula, Ejlertsen, Bent, Ekici, Arif B, Ellis, Steve, Elvira, Mingajeva, Eng, Kevin H, Engel, Christoph, Evans, D Gareth, Fasching, Peter A, Ferguson, Sarah, Ferrer, Sandra Fert, Flanagan, James M, Fogarty, Zachary C, Fortner, Renée T, Fostira, Florentia, Foulkes, William D, Fountzilas, George, Fridley, Brooke L, Friebel, Tara M, Friedman, Eitan, Frost, Debra, Ganz, Patricia A, Garber, Judy, García, María J, Garcia-Barberan, Vanesa, Gehrig, Andrea, Gentry-Maharaj, Aleksandra, Gerdes, Anne-Marie, Giles, Graham G, Glasspool, Rosalind, Glendon, Gord, Godwin, Andrew K, Goldgar, David E, Goranova, Teodora, Gore, Martin, Greene, Mark H, Gronwald, Jacek, Gruber, Stephen, Hahnen, Eric, Haiman, Christopher A, Håkansson, Niclas, Hamann, Ute, Hansen, Thomas V O, Harrington, Patricia A, Harris, Holly R, Hauke, Jan, Hein, Alexander, Henderson, Alex, Hildebrandt, Michelle A T, Hillemanns, Peter, Hodgson, Shirley, Høgdall, Claus K, Høgdall, Estrid, Hogervorst, Frans B L, Holland, Helene, Hooning, Maartje J, Hosking, Karen, Huang, Ruea-Yea, Hulick, Peter J, Hung, Jillian, Hunter, David J, Huntsman, David G, Huzarski, Tomasz, Imyanitov, Evgeny N, Isaacs, Claudine, Iversen, Edwin S, Izatt, Louise, Izquierdo, Angel, Jakubowska, Anna, James, Paul, Janavicius, Ramunas, Jernetz, Mats, Jensen, Allan, Jensen, Uffe Birk, John, Esther M, Johnatty, Sharon, Jones, Michael E, Kannisto, Päivi, Karlan, Beth Y, Karnezis, Anthony, Kast, Karin, Kennedy, Catherine J, Khusnutdinova, Elza, Kiemeney, Lambertus A, Kiiski, Johanna I, Kim, Sung-Won, Kjaer, Susanne K, Köbel, Martin, Kopperud, Reidun K, Kruse, Torben A, Kupryjanczyk, Jolanta, Kwong, Ava, Laitman, Yael, Lambrechts, Diether, Larrañaga, Nerea, Larson, Melissa C, Lazaro, Conxi, Le, Nhu D, Le Marchand, Loic, Lee, Jong Won, Lele, Shashikant B, Leminen, Arto, Leroux, Dominique, Lester, Jenny, Lesueur, Fabienne, Levine, Douglas A, Liang, Dong, Liebrich, Clemens, Lilyquist, Jenna, Lipworth, Loren, Lissowska, Jolanta, Lu, Karen H, Lubinński, Jan, Luccarini, Craig, Lundvall, Lene, Mai, Phuong L, Mendoza-Fandiño, Gustavo, Manoukian, Siranoush, Massuger, Leon F A G, May, Taymaa, Mazoyer, Sylvie, McAlpine, Jessica N, McGuire, Valerie, McLaughlin, John R, McNeish, Iain, Meijers-Heijboer, Hanne, Meindl, Alfons, Menon, Usha, Mensenkamp, Arjen R, Merritt, Melissa A, Milne, Roger L, Mitchell, Gillian, Modugno, Francesmary, Moes-Sosnowska, Joanna, Moffitt, Melissa, Montagna, Marco, Moysich, Kirsten B, Mulligan, Anna Marie, Musinsky, Jacob, Nathanson, Katherine L, Nedergaard, Lotte, Ness, Roberta B, Neuhausen, Susan L, Nevanlinna, Heli, Niederacher, Dieter, Nussbaum, Robert L, Odunsi, Kunle, Olah, Edith, Olopade, Olufunmilayo I, Olsson, Håkan, Olswold, Curtis, O'Malley, David M, Ong, Kai-ren, Onland-Moret, N Charlotte, Orr, Nicholas, Orsulic, Sandra, Osorio, Ana, Palli, Domenico, Papi, Laura, Park-Simon, Tjoung-Won, Paul, James, Pearce, Celeste L, Pedersen, Inge Søkilde, Peeters, Petra H M, Peissel, Bernard, Peixoto, Ana, Pejovic, Tanja, Pelttari, Liisa M, Permuth, Jennifer B, Peterlongo, Paolo, Pezzani, Lidia, Pfeiler, Georg, Phillips, Kelly-Anne, Piedmonte, Marion, Pike, Malcolm C, Piskorz, Anna M, Poblete, Samantha R, Pocza, Timea, Poole, Elizabeth M, Poppe, Bruce, Porteous, Mary E, Prieur, Fabienne, Prokofyeva, Darya, Pugh, Elizabeth, Pujana, Miquel Angel, Pujol, Pascal, Radice, Paolo, Rantala, Johanna, Rappaport-Fuerhauser, Christine, Rennert, Gad, Rhiem, Kerstin, Rice, Patricia, Richardson, Andrea, Robson, Mark, Rodriguez, Gustavo C, Rodríguez-Antona, Cristina, Romm, Jane, Rookus, Matti A, Rossing, Mary Anne, Rothstein, Joseph H, Rudolph, Anja, Runnebaum, Ingo B, Salvesen, Helga B, Sandler, Dale P, Schoemaker, Minouk J, Senter, Leigha, Setiawan, V Wendy, Severi, Gianluca, Sharma, Priyanka, Shelford, Tameka, Siddiqui, Nadeem, Side, Lucy E, Sieh, Weiva, Singer, Christian F, Sobol, Hagay, Song, Honglin, Southey, Melissa C, Spurdle, Amanda B, Stadler, Zsofia, Steinemann, Doris, Stoppa-Lyonnet, Dominique, Sucheston-Campbell, Lara E, Sukiennicki, Grzegorz, Sutphen, Rebecca, Sutter, Christian, Swerdlow, Anthony J, Szabo, Csilla I, Szafron, Lukasz, Tan, Yen Y, Taylor, Jack A, Tea, Muy-Kheng, Teixeira, Manuel R, Teo, Soo-Hwang, Terry, Kathryn L, Thompson, Pamela J, Thomsen, Liv Cecilie Vestrheim, Thull, Darcy L, Tihomirova, Laima, Tinker, Anna V, Tischkowitz, Marc, Tognazzo, Silvia, Toland, Amanda Ewart, Tone, Alicia, Trabert, Britton, Travis, Ruth C, Trichopoulou, Antonia, Tung, Nadine, Tworoger, Shelley S, van Altena, Anne M, Van Den Berg, David, van der Hout, Annemarie H, van der Luijt, Rob B, Van Heetvelde, Mattias, Van Nieuwenhuysen, Els, van Rensburg, Elizabeth J, Vanderstichele, Adriaan, Varon-Mateeva, Raymonda, Vega, Ana, Edwards, Digna Velez, Vergote, Ignace, Vierkant, Robert A, Vijai, Joseph, Vratimos, Athanassios, Walker, Lisa, Walsh, Christine, Wand, Dorothea, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Webb, Penelope M, Weinberg, Clarice R, Weitzel, Jeffrey N, Wentzensen, Nicolas, Whittemore, Alice S, Wijnen, Juul T, Wilkens, Lynne R, Wolk, Alicja, Woo, Michelle, Wu, Xifeng, Wu, Anna H, Yang, Hannah, Yannoukakos, Drakoulis, Ziogas, Argyrios, Zorn, Kristin K, Narod, Steven A, Easton, Douglas F, Amos, Christopher I, Schildkraut, Joellen M, Ramus, Susan J, Ottini, Laura, Goodman, Marc T, Park, Sue K, Kelemen, Linda E, Risch, Harvey A, Thomassen, Mads, Offit, Kenneth, Simard, Jacques, Schmutzler, Rita Katharina, Hazelett, Dennis, Monteiro, Alvaro N, Couch, Fergus J, Berchuck, Andrew, Chenevix-Trench, Georgia, Goode, Ellen L, Sellers, Thomas A, Gayther, Simon A, Antoniou, Antonis C, and Pharoah, Paul D P

Published
2017
Full Text
View/download PDF

13. Synchronous Ovarian and Breast Cancers with a Novel Variant in BRCA2 Gene: A Case Report

Author

Llinás-Quintero, Néstor, Cabrera-Florez, Eduardo, Mendoza-Fandiño, Gustavo, Matute-Turizo, Gustavo, Vasquez-Trespalacios, Elsa M., and Gallón-Villegas, Luis J.

Subjects
Article Subject
Abstract

We report a case of a 52-year-old female with a family history of pancreatic and colon cancers who presented with a right breast mass positive for high-grade medullar carcinoma with triple-negative biomolecular profile. Further workup was performed finding a left ovarian mass. The patient underwent laparotomy performing optimal cytoreduction on bilateral ovarian tumors; the pathology and immunohistochemistry confirmed bilateral ovary adenocarcinoma with positive peritoneal malignancy. Due to her synchronic breast and ovarian cancers, a genetic profile was performed detecting a new pathogenic variant in the BRCA2 gene: c.3606_3607del (p.Ser1203Cysfs). She was given chemotherapy with carboplatin and paclitaxel obtaining complete clinical response. Regarding her breast cancer, she had a right modified radical mastectomy and prophylactic left mastectomy obtaining complete clinical response. This case presents with an unusual subtype and difficult histologic diagnosis of a synchronic medullar breast cancer and ovary carcinoma associated with a new mutation of the BRCA2 gene.

Published
2019
Full Text
View/download PDF

14. Functional Analysis and Fine Mapping of the 9p22.2 Ovarian Cancer Susceptibility Locus

Author

Buckley, Melissa A, Woods, Nicholas T, Tyrer, Jonathan P, Mendoza-Fandiño, Gustavo, Lawrenson, Kate, Hazelett, Dennis J, Najafabadi, Hamed S, Gjyshi, Anxhela, Carvalho, Renato S, Lyra, Paulo C, Coetzee, Simon G, Shen, Howard C, Yang, Ally W, Earp, Madalene A, Yoder, Sean J, Risch, Harvey, Chenevix-Trench, Georgia, Ramus, Susan J, Phelan, Catherine M, Coetzee, Gerhard A, Noushmehr, Houtan, Hughes, Timothy R, Sellers, Thomas A, Goode, Ellen L, Pharoah, Paul D, Gayther, Simon A, Monteiro, Alvaro NA, Ovarian Cancer Association Consortium, Lawrenson, Kate [0000-0002-6469-2515], Hazelett, Dennis J [0000-0003-0749-9935], Najafabadi, Hamed S [0000-0003-2735-4231], Coetzee, Simon G [0000-0003-4267-5930], Yoder, Sean J [0000-0003-0005-7798], Coetzee, Gerhard A [0000-0003-4267-5930], Noushmehr, Houtan [0000-0003-4051-8114], and Apollo - University of Cambridge Repository

Subjects
Ovarian Cancer Association Consortium, Oncology and Carcinogenesis, Cystadenocarcinoma, Cell Cycle Proteins, Carcinoma, Ovarian Epithelial, Polymorphism, Single Nucleotide, Chromosomes, Linkage Disequilibrium, Cell Line, Rare Diseases, Ovarian Epithelial, Cell Line, Tumor, Genetics, 2.1 Biological and endogenous factors, Humans, Genetic Predisposition to Disease, Oncology & Carcinogenesis, Polymorphism, Aetiology, Cancer, Ovarian Neoplasms, Tumor, Base Sequence, Prevention, Carcinoma, Human Genome, Serous, Chromosome Mapping, DNA, Single Nucleotide, DNA, Neoplasm, Ovarian Cancer, Cystadenocarcinoma, Serous, DNA-Binding Proteins, HEK293 Cells, Neoplasm, Female, Chromosomes, Human, Pair 9, Human, Pair 9, Biotechnology, Genome-Wide Association Study
Abstract

Genome-wide association studies have identified 40 ovarian cancer risk loci. However, the mechanisms underlying these associations remain elusive. In this study, we conducted a two-pronged approach to identify candidate causal SNPs and assess underlying biological mechanisms at chromosome 9p22.2, the first and most statistically significant associated locus for ovarian cancer susceptibility. Three transcriptional regulatory elements with allele-specific effects and a scaffold/matrix attachment region were characterized and, through physical DNA interactions, BNC2 was established as the most likely target gene. We determined the consensus binding sequence for BNC2 in vitro, verified its enrichment in BNC2 ChIP-seq regions, and validated a set of its downstream target genes. Fine-mapping by dense regional genotyping in over 15,000 ovarian cancer cases and 30,000 controls identified SNPs in the scaffold/matrix attachment region as among the most likely causal variants. This study reveals a comprehensive regulatory landscape at 9p22.2 and proposes a likely mechanism of susceptibility to ovarian cancer. SIGNIFICANCE: Mapping the 9p22.2 ovarian cancer risk locus identifies BNC2 as an ovarian cancer risk gene.See related commentary by Choi and Brown, p. 439.

Published
2018
Full Text
View/download PDF

15. Memorias VIII Encuentro Nacional Semilleros de Investigación

Author

Pérez Velandia, Angie Zuleima, primary, Matéus Montañez, Luis Fernando, additional, Fuquen, Henry, additional, Gómez Gómez, Duván Leonardo, additional, Valencia Marín, Jhon Mario, additional, Arismendy García, Carlos Enrique, additional, Pérez, Brayan Felipe, additional, Criollo Perdomo, Harol Tiberio, additional, Rodríguez Gaitán, Ginneth, additional, Niquepa Gordillo, Andrés, additional, Pastrana Pastrana, Sergio Andrés, additional, Contreras Jáuregui, Angélica María, additional, Escudero Paniagua, Alejandro, additional, Toro Gil, Cristian, additional, Muñoz Muñoz, Jéssica, additional, Buitrago, John Sebastián, additional, González Olaya, Hugo de Jesús, additional, Restrepo Alarcón, Carlos Alberto, additional, Alba Granados, Luis Andrés, additional, Romero Mendoza, Juan Pablo, additional, García, Juan José, additional, Campillo-Machado, Francisco, additional, Rodríguez, Anderson A., additional, Cardona, Alejandro, additional, Urrea, Diana María, additional, Narváez, Jhon Fredy, additional, Cano González, Mateo, additional, Restrepo Ocampo, Lorena, additional, Ramírez López, Jackeline, additional, Arias Herrera, Natalia, additional, Franco Aristizábal, Valeria, additional, Vallejo Arbeláez, Diereck, additional, Ramírez Jiménez, Sandra Liliana, additional, Bermúdez Manzano, Lina María, additional, Baena Valencia, Beatriz Elena, additional, Avendaño Osorio, Yuber, additional, Ochoa Madera, Laura, additional, Hurtado, Juan David, additional, Pérez Velásquez, Natalia Estefany, additional, Roa Camargo, Mauro Sebastián, additional, Alfonso Romero, Jhon Jairo, additional, Camargo Botiva, Nelson Hernando, additional, Pérez Walteros, Orlando, additional, Marín Gallo, Jurany, additional, Gallego López, Andrés Felipe, additional, Carvajal Galvis, Jorge Andrés, additional, Bustamante, María Alejandra, additional, Ardila, Daniel, additional, Pérez, Juliana, additional, Bolívar Hernández, Carlos Mario, additional, Ruiz Montoya, Sara, additional, Zapata, Sandra Milena, additional, Taborda Quintero, Juan David, additional, Alarcón A., Lina, additional, Gallego, Deissy Milena, additional, Ángel G., Julio César, additional, Barrera Tangarife, Jenny Johana, additional, Restrepo Foronda, Juan Carlos, additional, Baena Robledo, Natalia, additional, Mesa, Óscar, additional, Correa, Celsa Lucía, additional, Montoya Hoyos, Pablo, additional, Medina Castaño, Julio Fernando, additional, Galvis, Leidy Tatiana, additional, Castaño Zea, Lina Marcela, additional, Bedoya Escobar, Héctor Iván, additional, Cuervo Puerta, Gonzalo Andrés, additional, Domínguez Urrego, Alexandra María, additional, Henao Vargas, Yeidi Melisa, additional, Orrego Lombana, Gerardo, additional, Velásquez López, José Daniel, additional, Paguana, Luis Fernando, additional, Patiño Bedoya, Guisier Astrid, additional, Agudelo González, Marisol, additional, Boss Agudelo, Jovanny, additional, Botero-Botero, Luis, additional, Pérez-Pérez, Juliana, additional, Quintero-Reyes, Carlos, additional, Duque-Vásquez, Diego Alejandro, additional, Henao Villa, María Eucaris, additional, Uribe Espinosa, Stiv, additional, Rendón Saraza, Lisandro Arley, additional, Gutiérrez, Johanna Andrea, additional, Valencia Soto, Yeferson Daniel, additional, Jiménez-Quintero, Santiago, additional, Montoya-González, Duván Alberto, additional, Calvo, Víctor Daniel, additional, Garrido-Zea, Érika Francisca, additional, Gaviria-Cortés, Óscar Ómar, additional, Calderón Parra, Daniela Alejandra, additional, Restrepo Montoya, Laura, additional, Cardona Jiménez, Jairo León, additional, Metrio-Jiménez, Melissa, additional, Buitrago-Muñoz, Yuly N., additional, Marín Peláez, Yamile Yulied, additional, Osorio Morales, Yorleida, additional, Villa Pulgarin, Janny A., additional, Gallo Naranjo, Laura, additional, Ríos Botero, Diana, additional, Sandoval Sánchez, Jairo, additional, Villalobo Parra, Estefanía, additional, Fuentes Ávila, Keisy Esteban, additional, Calvo, Víctor, additional, Orozco, Santiago, additional, Sánchez, Isaura Pilar, additional, Ortiz Cano, Alexis, additional, Millán Zapata, Carlos, additional, Arias Pérez, Rubén Darío, additional, Carvajal Mejía, Sara Manuela, additional, González Serna, Nicole Andrea, additional, Gallego Quintero, Salomón, additional, Patiño Isaza, Ana María, additional, Flórez Restrepo, Daniela Lucía, additional, Alzate Ángel, Juan Carlos, additional, Taborda Vanegas, Natalia Andrea, additional, Correa Mejía, Juliana, additional, Amaya Ocampo, Heyner, additional, Loaiza Mejía, María Camila, additional, Villalba Galvis, Ania Alejandra, additional, Escudero Cardona, Diana Elizabeth, additional, López, María Elena, additional, Gallego, Sebastián, additional, Ortiz Vásquez, Alejandra, additional, Rivera, Julián, additional, Atehortúa Hernández, Geraldine, additional, Tamayo Rendón, Melisa Andrea, additional, Valencia Hernández, María de Jesús, additional, Osorno Avendaño, Daniela, additional, Castaño Ramírez, Estefanía, additional, Quintero Echeverri, Ángela, additional, Correa, Angie Paola, additional, Patiño Rendón, Jessica, additional, Cano, Carolina, additional, Urrego Galeano, María Johana, additional, Padilla Rendón, Yarledis, additional, Bedoya Cano, Daniela, additional, Cardona Puerta, Andrés Felipe, additional, Medina Gaviria, Kevin David, additional, Arévalo Burbano, Héctor René, additional, Gómez Hernández, Carlos Andrés, additional, García Alarcón, Mariana, additional, Carrillo, María Cecilia, additional, Maya, Ana María, additional, de Sousa Muñoz, Keythy Helen, additional, Yepes Cano, Germán Sebastián, additional, Ramírez Salazar, Daniela Andrea, additional, Agudelo Marín, Yohana Cirley, additional, Quirós Montoya, Pedro Luis, additional, Bedoya Carvajal, Óscar Augusto, additional, Camacho López, Natalia, additional, Marín Zapata, Diana Carolina, additional, Rivas Rentería, Neisi Jackelina, additional, Villalba Barón, Luz Dary, additional, Rivera Cardona, Cristian Felipe, additional, Romaña Mosquera, Darlen Daniza, additional, Ciro, Lina Marcela, additional, Sánchez, Elsa Yolanda, additional, Atehortúa Agudelo, Yasmín, additional, Jiménez Zapata, Esteban, additional, Giraldo Gómez, Deisy Jhoana, additional, Carmona Múnera, Geraldin, additional, Vélez Castañeda, Jéssica María, additional, Rueda Guiral, Leydy Johana, additional, Rivera, Cristian Felipe, additional, Taborda Rengifo, Julián, additional, Muñetón Franco, Cristian, additional, Villamizar Montagut, Angélica María, additional, Jiménez Roldán, Sara, additional, Sánchez Acevedo, Katherine, additional, Betancourt Pantoja, María Alejandra, additional, Córdoba Castillo, Lina, additional, Barón Castaño, Andrés Felipe, additional, Manco Saldarriaga, Estefanía, additional, García Flórez, Laura Fabiola, additional, Castro Álvarez, John Fredy, additional, Taborda Agudelo, Sindy Johana, additional, Padierna Ortiz, Yurany, additional, Arteaga, Aníbal, additional, Villa, Janny Alexander, additional, Ospina Sánchez, Waira, additional, Moreno Delgado, Maide Yhurany, additional, Uribe, Andrea Catalina, additional, Echavarría, Gladys del Socorro, additional, Arango Agudelo, Laura María, additional, Morales Montoya, Juliana, additional, Velásquez V., Juliana, additional, Torres, Carolina, additional, Cárdenas, Estefanía, additional, Loaiza G., Leydi Maryoris, additional, Puello B., Maryolis, additional, Jaramillo González, Deisy Jazmín, additional, Duque Ramírez, María Fernanda, additional, Gaona Narváez, Yira, additional, Delgado Jiménez, Carlos Eugenio, additional, Jaramillo, Andrés, additional, Cadavid, Felipe, additional, Duque Q., Mónica, additional, Areiza, Harold, additional, Jaramillo, Carlos David, additional, Hoyos, Álvaro, additional, Vásquez Mejía, Emely Johanna, additional, Gil, Luisa Fernanda, additional, Escobar Salazar, Sara, additional, Gómez-Ruiz, Daisy Alejandra, additional, Cadavid-Ramírez, Ana Cristina, additional, Castaño-González, Ana Lucía, additional, León, Santiago, additional, Zambrano, Melissa, additional, Escobar, Juan David, additional, Gómez Velilla, Santiago, additional, Ortiz, Tatiana, additional, García Gutiérrez, Robinson Daniel, additional, Omaña García, Julia Victoria, additional, Uribe Giraldo, Sara Melissa, additional, Saldarriaga, Santiago, additional, Londoño Pérez, Jhonny, additional, Castaño, Ana Lucía, additional, Mazo, Raúl, additional, Tamayo, Juanita, additional, Echeverry, Maribel, additional, Correa, Sergio Andrés, additional, Zambrano, Ricardo, additional, Salazar Torres, Lina María, additional, García González, Daniela, additional, Espinoza Gómez, María Paz, additional, Buitrago Mejía, Jhonny Alberto, additional, Trujillo Hincapié, Daniela, additional, Oliveros, Andrés Giovanni, additional, Gallego Rodríguez, Renso Sneider, additional, Ospina Barrera, Daniela, additional, Monsalve, Juan David, additional, Leysner Tavera, Jesika, additional, Zambrano, Erwin Ricardo, additional, Luján, Juan Diego, additional, Hernández, Samuel Etien, additional, Marín López, Sergio, additional, Correa Muñoz, Daniel Camilo, additional, Gómez, Daisy Alejandra, additional, Marín Villa, Julián, additional, Duque, Laura, additional, Mendoza Fandiño, Gustavo Alfonso, additional, Herrera, Bryan, additional, Duque, Sandra Patricia, additional, Naranjo Agudelo, Jhon Fredy, additional, Herrera Mesa, Sarita, additional, Gómez Valencia, Jhonatan Andrés, additional, Álvarez Arroyave, Laura Carolina, additional, Builes Rodríguez, Juan Carlos, additional, Bedoya Giraldo, Sara, additional, Cantor García, Paola, additional, Sánchez Zapata, Gloria Y., additional, Patiño Posada, José I., additional, Saldarriaga Palacio, Sara, additional, Palacio Pareja, Juan Pablo, additional, Buitrago, Jhonny Alberto, additional, Chaux, María A., additional, Cubillos, Oscar E., additional, Lobo, Hernán D., additional, Sánchez, Gerardo, additional, Gallego, Jorge Enrique, additional, Velásquez, Laura Yesenia, additional, Morales Gómez, Simón, additional, López, Manuela, additional, Villanueva, Neidy, additional, Aguirre, Julio César, additional, Betancur Ospina, Daniela, additional, Gómez Noreña, Manuela, additional, Agudelo Marín, Verónica Tatiana, additional, Rojas Zapata, María Alejandra, additional, Rúa Gómez, María Alejandra, additional, Sepúlveda Correa, Manuela, additional, Echeverri Alzate, Sara, additional, Jaramillo Restrepo, Maribel, additional, Martínez Granada, Manuela, additional, Echeverri Hernández, Maribel, additional, and Céspedes Mesa, Gabriel, additional

Published
2019
Full Text
View/download PDF

18. Enhancer scanning to locate regulatory regions in genomic loci

Author

Buckley, Melissa, Gjyshi, Anxhela, Mendoza-Fandiño, Gustavo, Baskin, Rebekah, Carvalho, Renato S, Carvalho, Marcelo A, Woods, Nicholas T, and Monteiro, Alvaro N A

Abstract

This protocol provides a rapid, streamlined and scalable strategy to systematically scan genomic regions for the presence of transcriptional regulatory regions that are active in a specific cell type. It creates genomic tiles spanning a region of interest that are subsequently cloned by recombination into a luciferase reporter vector containing the simian virus 40 promoter. Tiling clones are transfected into specific cell types to test for the presence of transcriptional regulatory regions. The protocol includes testing of different single-nucleotide polymorphism (SNP) alleles to determine their effect on regulatory activity. This procedure provides a systematic framework for identifying candidate functional SNPs within a locus during functional analysis of genome-wide association studies. This protocol adapts and combines previous well-established molecular biology methods to provide a streamlined strategy, based on automated primer design and recombinational cloning, allowing one to rapidly go from a genomic locus to a set of candidate functional SNPs in 8 weeks.

Published
2016
Full Text
View/download PDF

19. Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer

Author

Couch, Fergus J., Kuchenbaecker, Karoline B., Michailidou, Kyriaki, Mendoza-Fandino, Gustavo A., Nord, Silje, Lilyquist, Janna, Olswold, Curtis, Hallberg, Emily, Agata, Simona, Ahsan, Habibul, Aittomäki, Kristiina, Ambrosone, Christine, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Arun, Banu K., Arver, Brita, Barile, Monica, Barkardottir, Rosa B., Barrowdale, Daniel, Beckmann, Lars, Beckmann, Matthias W., Benitez, Javier, Blank, Stephanie V., Blomqvist, Carl, Bogdanova, Natalia V., Bojesen, Stig E., Bolla, Manjeet K., Bonanni, Bernardo, Brauch, Hiltrud, Brenner, Hermann, Burwinkel, Barbara, Buys, Saundra S., Caldes, Trinidad, Caligo, Maria A., Canzian, Federico, Carpenter, Jane, Chang-Claude, Jenny, Chanock, Stephen J., Chung, Wendy K., Claes, Kathleen B. M., Cox, Angela, Cross, Simon S., Cunningham, Julie M., Czene, Kamila, Daly, Mary B., Damiola, Francesca, Darabi, Hatef, de la Hoya, Miguel, Devilee, Peter, Diez, Orland, Ding, Yuan C., Dolcetti, Riccardo, Domchek, Susan M., Dorfling, Cecilia M., dos-Santos-Silva, Isabel, Dumont, Martine, Dunning, Alison M., Eccles, Diana M., Ehrencrona, Hans, Ekici, Arif B., Eliassen, Heather, Ellis, Steve, Fasching, Peter A., Figueroa, Jonine, Flesch-Janys, Dieter, Försti, Asta, Fostira, Florentia, Foulkes, William D., Friebel, Tara, Friedman, Eitan, Frost, Debra, Gabrielson, Marike, Gammon, Marilie D., Ganz, Patricia A., Gapstur, Susan M., Garber, Judy, Gaudet, Mia M., Gayther, Simon A., Gerdes, Anne-Marie, Ghoussaini, Maya, Giles, Graham G., Glendon, Gord, Godwin, Andrew K., Goldberg, Mark S., Goldgar, David E., González-Neira, Anna, Greene, Mark H., Gronwald, Jacek, Guénel, Pascal, Gunter, Marc, Haeberle, Lothar, Haiman, Christopher A., Hamann, Ute, Hansen, Thomas V. O., Hart, Steven, Healey, Sue, Heikkinen, Tuomas, Henderson, Brian E., Herzog, Josef, Hogervorst, Frans B. L., Hollestelle, Antoinette, Hooning, Maartje J., Hoover, Robert N., Hopper, John L., Humphreys, Keith, Hunter, David J., Huzarski, Tomasz, Imyanitov, Evgeny N., Isaacs, Claudine, Jakubowska, Anna, James, Paul, Janavicius, Ramunas, Jensen, Uffe Birk, John, Esther M., Jones, Michael, Kabisch, Maria, Kar, Siddhartha, Karlan, Beth Y., Khan, Sofia, Khaw, Kay-Tee, Kibriya, Muhammad G., Knight, Julia A., Ko, Yon-Dschun, Konstantopoulou, Irene, Kosma, Veli-Matti, Kristensen, Vessela, Kwong, Ava, Laitman, Yael, Lambrechts, Diether, Lazaro, Conxi, Lee, Eunjung, Le Marchand, Loic, Lester, Jenny, Lindblom, Annika, Lindor, Noralane, Lindstrom, Sara, Liu, Jianjun, Long, Jirong, Lubinski, Jan, Mai, Phuong L., Makalic, Enes, Malone, Kathleen E., Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Marme, Frederik, Martens, John W. M., McGuffog, Lesley, Meindl, Alfons, Miller, Austin, Milne, Roger L., Miron, Penelope, Montagna, Marco, Mazoyer, Sylvie, Mulligan, Anna M., Muranen, Taru A., Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Nordestgaard, Børge G., Nussbaum, Robert L., Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo I., Olson, Janet E., Osorio, Ana, Park, Sue K., Peeters, Petra H., Peissel, Bernard, Peterlongo, Paolo, Peto, Julian, Phelan, Catherine M., Pilarski, Robert, Poppe, Bruce, Pylkäs, Katri, Radice, Paolo, Rahman, Nazneen, Rantala, Johanna, Rappaport, Christine, Rennert, Gad, Richardson, Andrea, Robson, Mark, Romieu, Isabelle, Rudolph, Anja, Rutgers, Emiel J., Sanchez, Maria-Jose, Santella, Regina M., Sawyer, Elinor J., Schmidt, Daniel F., Schmidt, Marjanka K., Schmutzler, Rita K., Schumacher, Fredrick, Scott, Rodney, Senter, Leigha, Sharma, Priyanka, Simard, Jacques, Singer, Christian F., Sinilnikova, Olga M., Soucy, Penny, Southey, Melissa, Steinemann, Doris, Stenmark-Askmalm, Marie, Stoppa-Lyonnet, Dominique, Swerdlow, Anthony, Szabo, Csilla I., Tamimi, Rulla, Tapper, William, Teixeira, Manuel R., Teo, Soo-Hwang, Terry, Mary B., Thomassen, Mads, Thompson, Deborah, Tihomirova, Laima, Toland, Amanda E., Tollenaar, Robert A. E. M., Tomlinson, Ian, Truong, Thérèse, Tsimiklis, Helen, Teulé, Alex, Tumino, Rosario, Tung, Nadine, Turnbull, Clare, Ursin, Giski, van Deurzen, Carolien H. M., van Rensburg, Elizabeth J., Varon-Mateeva, Raymonda, Wang, Zhaoming, Wang-Gohrke, Shan, Weiderpass, Elisabete, Weitzel, Jeffrey N., Whittemore, Alice, Wildiers, Hans, Winqvist, Robert, Yang, Xiaohong R., Yannoukakos, Drakoulis, Yao, Song, Zamora, M Pilar, Zheng, Wei, Hall, Per, Kraft, Peter, Vachon, Celine, Slager, Susan, Chenevix-Trench, Georgia, Pharoah, Paul D. P., Monteiro, Alvaro A. N., García-Closas, Montserrat, Easton, Douglas F., and Antoniou, Antonis C.

Abstract

Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 × 10−8) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for ∼11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.

Published
2016
Full Text
View/download PDF

20. Detection of genetic variants in the BRCA1 and BRCA2 genes in canines with mammary neoplasms in the Metropolitan Area - Antioquia, Colombia and their correlation with the histological type

Author

Arango Vásquez, Luiggi Mateo, Mendoza Fandiño, Gustavo Alfonso, and Muñetón Peña, Carlos Mario

Subjects
Mammary neoplasms, animal, Histology, id.nlm.nih.gov/mesh/D019313 [http], Patología veterinaria, Proteina BRCA1, id.nlm.nih.gov/mesh/D024682 [http], Histología, Variación genética, id.nlm.nih.gov/mesh/D008321 [http], id.nlm.nih.gov/mesh/D014644 [http], id.nlm.nih.gov/mesh/D006653 [http], Pathology, veterinary, Mammary glands, animal, Glándulas mamarias animales, Neoplasias mamarias animales, id.nlm.nih.gov/mesh/D015674 [http], Proteína BRCA2, id.nlm.nih.gov/mesh/D010341 [http], Genetic variation, BRCA2 protein, BRCA1 protein, Área metropolitana, Medellín
Abstract

RESUMEN: Las neoplasias son procesos patológicos multifactoriales caracterizados por la proliferación anormal e incontrolada de las células. Las neoplasias mamarias son diagnosticadas comúnmente en las hembras caninas no esterilizadas con reportes epidemiológicos entre el 20,5% y el 70,5% dependiendo de la población estudiada. Las neoplasias mamarias presentan una alta heterogeneidad histológica debido a sus múltiples componentes celulares. Diferentes factores intervienen en la pérdida del control de la proliferación celular. Se han reportado variantes genéticas en los genes Breast Cáncer type 1 (BRCA1) Breast Cáncer type 2 (BRCA2) relacionadas con el desarrollo de neoplasias mamarias en caninos. BRCA1 y BRCA2 son genes supresores tumorales cuya función es la regulación de la proliferación celular, reparación del daño por rupturas en la doble cadena de DNA y el mantenimiento de la estabilidad genómica. Actualmente en Colombia no existen reportes de estudios que detecten la presencia y establezcan la frecuencia de variantes genéticas en los genes BRCA1 y BRCA2 relacionadas con las neoplasias mamarias en caninos. El objetivo de este estudio fue determinar la presencia y frecuencia de las variantes genéticas identificadas previamente en la literatura, c.4762 G>T p.W1567STOP en el exón 13 del gen BRCA1 y c.2401 A>C p.K801Q, c.2488 A>G p.I830V, c.4273 A>C p.T1425P y c.4304 A>G p.K1435R ubicadas en el exón 11 del gen BRCA2 en 75 caninos hembra con neoplasias mamarias del Área metropolitana; Antioquia, caracterizar histopatológicamente sus tejidos neoplásicos mamarios y establecer la relación entre la presencia de las variantes genéticas y características como el tipo histológico, la edad, la raza entre otras. Se encontraron 8 diferentes tipos histológicos en los tejidos neoplásicos mamarios estudiados, 7 clasificados como malignos, siendo el carcinoma mixto mamario el más común con un 36%. Las frecuencias de las variantes genéticas estudiadas fueron: 65.3% p.K1435R, 51.9% p.K801Q, 13.3% p.T1425P y 5.3% p.I830V. Adicional se establecieron los diferentes haplotipos según las combinaciones alélicas, 5 en total, de los cuales el CAAA que presentaba la variante p.K801Q en condición homocigota se relacionó estadísticamente significativa con el tipo histológico y la raza. También se encontró que los individuos con la variante genética c.2401 A>C p.K801Q en condición homocigota presentaron una mediana de edad de aparición de la neoplasia mamaria menor, en 2.5 años, respecto al resto de individuos de la población de estudio, siendo esto estadísticamente significativo. Estos hallazgos permiten establecer un primer registro epidemiológico y molecular sobre la presencia de variantes genéticas en los genes BRCA1 y BRCA2, relacionadas con el desarrollo de neoplasias mamarias en caninos en el Área Metropolitana de Antioquia, Colombia, las cuales presentan una relación con características neoplásicas y poblacionales. Este estudio estableció por primera vez una relación genotipo - fenotipo en el cáncer de mama en caninos en Colombia. ABSTRAC: Neoplasms are multifactorial pathological processes characterized by abnormal and uncontrolled proliferation of cells. Mammary neoplasms are commonly diagnosed in non-sterilized canine females with epidemiological reports between 20.5% and 70.5% depending on the population studied. Breast neoplasms present a high histological heterogeneity due to their multiple cellular and histological components. Different factors intervene in the loss of control of cell proliferation. Genetic variants have been reported in Breast Cancer type 1 (BRCA1) and Breast Cancer type 2 (BRCA2) genes related to the development of mammary neoplasms in canines. BRCA1 and BRCA2 are tumor suppressor genes whose function is the regulation of cell proliferation, repair of damage due to breaks in the double strand of DNA and the maintenance of genomic stability. Currently in Colombia there are no reports of studies that detect the presence and establish the frequency of genetic variants in the BRCA1 and BRCA2 genes related to mammary neoplasms in canines. The objective of this study was to determine the presence and frequency of the genetic variants previously identified in the literature, c.4762 G> T p.W1567STOP in exon 13 of the BRCA1 gene and c.2401 A> C p.K801Q, c. 2488 A> G p.I830V, c.4273 A> C p.T1425P and c.4304 A> G p.K1435R located in exon 11 of the BRCA2 gene in 75 female canines with mammary neoplasms from the Metropolitan Area; Antioquia, histopathologically characterize its mammary neoplasm tissues and establish the relationship between the presence of genetic variants and characteristics such as histological type, age, race, among others. Eight different histological types were found in the studied mammary neoplasm tissues, 7 classified as malignant, with mixed mammary carcinoma being the most common with 36%. The frequencies of the genetic variants studied were: 65.3% p.K1435R, 51.9% p.K801Q, 13.3% p.T1425P and 5.3% p.I830V. In addition, the different haplotypes were established according to the allelic combinations, 5 in total, of which the CAAA that presented the p.K801Q variant in homozygous condition was statistically significant related to the histological type and race. It was also found that individuals with the genetic variant c.2401 A> C p.K801Q in a homozygous condition had a median age of appearance of the lower mammary neoplasm, in 2.5 years, compared to the rest of the individuals in the study population. this being statistically significant. These findings allow us to establish a first epidemiological and molecular registry on the presence of genetic variants in the BRCA1 and BRCA2 genes, related to the development of mammary neoplasms in canines in Colombia, which present a relationship with neoplasic and population characteristics. This study established for the first time a genotype-phenotype relationship in canine breast cancer in Colombia

Published
2021

Catalog

Books, media, physical & digital resources
See catalog results