Detectable clonal mosaicism and its relationship to aging and cancer

In an analysis of 31,717 cancer cases and 26,136 cancer-free controls drawn from 13 genome-wide association studies (GWAS), we observed large chromosomal abnormalities in a subset of clones from DNA obtained from blood or buccal samples. Mosaic chromosomal abnormalities, either aneuploidy or copy-ne...

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Detalles Bibliográficos
Autores principales: Jacobs, Kevin B, Yeager, Meredith, Zhou, Weiyin, Wacholder, Sholom, Wang, Zhaoming, Rodriguez-Santiago, Benjamin, Hutchinson, Amy, Deng, Xiang, Liu, Chenwei, Horner, Marie-Josephe, Cullen, Michael, Epstein, Caroline G, Burdett, Laurie, Dean, Michael C, Chatterjee, Nilanjan, Sampson, Joshua, Chung, Charles C, Kovaks, Joseph, Gapstur, Susan M, Stevens, Victoria L, Teras, Lauren T, Gaudet, Mia M, Albanes, Demetrius, Weinstein, Stephanie J, Virtamo, Jarmo, Taylor, Philip R, Freedman, Neal D, Abnet, Christian C, Goldstein, Alisa M, Hu, Nan, Yu, Kai, Yuan, Jian-Min, Liao, Linda, Ding, Ti, Qiao, You-Lin, Gao, Yu-Tang, Koh, Woon-Puay, Xiang, Yong-Bing, Tang, Ze-Zhong, Fan, Jin-Hu, Aldrich, Melinda C, Amos, Christopher, Blot, William J, Bock, Cathryn H, Gillanders, Elizabeth M, Harris, Curtis C, Haiman, Christopher A, Henderson, Brian E, Kolonel, Laurence N, Le Marchand, Loic, McNeill, Lorna H, Rybicki, Benjamin A, Schwartz, Ann G, Signorello, Lisa B, Spitz, Margaret R, Wiencke, John K, Wrensch, Margaret, Wu, Xifeng, Zanetti, Krista A, Ziegler, Regina G, Figueroa, Jonine D, Garcia-Closas, Montserrat, Malats, Nuria, Marenne, Gaelle, Prokunina-Olsson, Ludmila, Baris, Dalsu, Schwenn, Molly, Johnson, Alison, Landi, Maria Teresa, Goldin, Lynn, Consonni, Dario, Bertazzi, Pier Alberto, Rotunno, Melissa, Rajaraman, Preetha, Andersson, Ulrika, Freeman, Laura E Beane, Berg, Christine D, Buring, Julie E, Butler, Mary A, Carreon, Tania, Feychting, Maria, Ahlbom, Anders, Gaziano, J Michael, Giles, Graham G, Hallmans, Goran, Hankinson, Susan E, Hartge, Patricia, Henriksson, Roger, Inskip, Peter D, Johansen, Christoffer, Landgren, Annelie, McKean-Cowdin, Roberta, Michaud, Dominique S, Melin, Beatrice S, Peters, Ulrike, Ruder, Avima M, Sesso, Howard D, Severi, Gianluca, Shu, Xiao-Ou, Visvanathan, Kala, White, Emily, Wolk, Alicja, Zeleniuch-Jacquotte, Anne, Zheng, Wei, Silverman, Debra T, Kogevinas, Manolis, Gonzalez, Juan R, Villa, Olaya, Li, Donghui, Duell, Eric J, Risch, Harvey A, Olson, Sara H, Kooperberg, Charles, Wolpin, Brian M, Jiao, Li, Hassan, Manal, Wheeler, William, Arslan, Alan A, Bas Bueno-de-Mesquita, H, Fuchs, Charles S, Gallinger, Steven, Gross, Myron D, Holly, Elizabeth A, Klein, Alison P, LaCroix, Andrea, Mandelson, Margaret T, Petersen, Gloria, Boutron-Ruault, Marie-Christine, Bracci, Paige M, Canzian, Federico, Chang, Kenneth, Cotterchio, Michelle, Giovannucci, Edward L, Goggins, Michael, Bolton, Judith A Hoffman, Jenab, Mazda, Khaw, Kay-Tee, Krogh, Vittorio, Kurtz, Robert C, McWilliams, Robert R, Mendelsohn, Julie B, Rabe, Kari G, Riboli, Elio, Tjønneland, Anne, Tobias, Geoffrey S, Trichopoulos, Dimitrios, Elena, Joanne W, Yu, Herbert, Amundadottir, Laufey, Stolzenberg-Solomon, Rachael Z, Kraft, Peter, Schumacher, Fredrick, Stram, Daniel, Savage, Sharon A, Mirabello, Lisa, Andrulis, Irene L, Wunder, Jay S, García, Ana Patiño, Sierrasesúmaga, Luis, Barkauskas, Donald A, Gorlick, Richard G, Purdue, Mark, Chow, Wong-Ho, Moore, Lee E, Schwartz, Kendra L, Davis, Faith G, Hsing, Ann W, Berndt, Sonja I, Black, Amanda, Wentzensen, Nicolas, Brinton, Louise A, Lissowska, Jolanta, Peplonska, Beata, McGlynn, Katherine A, Cook, Michael B, Graubard, Barry I, Kratz, Christian P, Greene, Mark H, Erickson, Ralph L, Hunter, David J, Thomas, Gilles, Hoover, Robert N, Real, Francisco X, Fraumeni, Joseph F, Caporaso, Neil E, Tucker, Margaret, Rothman, Nathaniel, Pérez-Jurado, Luis A, Chanock, Stephen J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2012
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3372921/
https://www.ncbi.nlm.nih.gov/pubmed/22561519
http://dx.doi.org/10.1038/ng.2270
Descripción
Sumario:In an analysis of 31,717 cancer cases and 26,136 cancer-free controls drawn from 13 genome-wide association studies (GWAS), we observed large chromosomal abnormalities in a subset of clones from DNA obtained from blood or buccal samples. Mosaic chromosomal abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of size >2 Mb were observed in autosomes of 517 individuals (0.89%) with abnormal cell proportions between 7% and 95%. In cancer-free individuals, the frequency increased with age; 0.23% under 50 and 1.91% between 75 and 79 (p=4.8×10(−8)). Mosaic abnormalities were more frequent in individuals with solid-tumors (0.97% versus 0.74% in cancer-free individuals, OR=1.25, p=0.016), with a stronger association for cases who had DNA collected prior to diagnosis or treatment (OR=1.45, p=0.0005). Detectable clonal mosaicism was common in individuals for whom DNA was collected at least one year prior to diagnosis of leukemia compared to cancer-free individuals (OR=35.4, p=3.8×10(−11)). These findings underscore the importance of the role and time-dependent nature of somatic events in the etiology of cancer and other late-onset diseases.

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