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Detectable clonal mosaicism and its relationship to aging and cancer
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In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of > 2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 x 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 x 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.
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JACOBS, Kevin b., YEAGER, Meredith, ZHOU, Weiyin, WACHOLDER, Sholom, WANG, Zhaoming, RODRÍGUEZ SANTIAGO, Benjamín, HUTCHINSON, Amy, DENG, Xiang, LIU, Chenwei, HORNER, Marie-josephe, CULLEN, Michael, SIGNORELLO, Lisa b., TUCKER, Margaret, DING, Ti, LANDGREN, Annelie, ALDRICH, Melinda c., STRAM, Daniel, HENRIKSSON, Roger, KRAFT, Peter, HENDERSON, Brian e., STOLZENBERG-SOLOMON, Rachael z., BERTAZZI, Pier alberto, HU, Nan, SCHWENN, Molly, XIANG, Yong-bing, GROSS, Myron d., KOGEVINAS, Manolis, BOCK, Cathryn h., EPSTEIN, Caroline g., PURDUE, Mark p., QIAO, You-lin, PATIÑO GARCÍA, Ana, CHANOCK, Stephen j., KOOPERBERG, Charles, CANZIAN, Federico, AHLBOM, Anders, KHAW, Kay-tee, HASSAN, Manal, VILLA, Olaya, GIOVANNUCCI, Edward l., SHU, Xiao-ou, GAUDET, Mia m., KLEIN, Alison p., ERICKSON, Ralph l., COOK, Michael b., RUDER, Avima m., ZELENIUCH-JACQUOTTE, Anne, CHATTERJEE, Nilanjan, GOGGINS, Michael, CHANG, Kenneth, WIENCKE, John k., GAPSTUR, Susan m., REAL, Francisco x., ZANETTI, Krista a., GORLICK, Richard g., WUNDER, Jay s., WHEELER, William, SCHUMACHER, Fredrick, GONZALEZ, Juan r., GALLINGER, Steven, FAN, Jin-hu, ZHENG, Wei, PEPLONSKA, Beata, LANDI, Maria teresa, THOMAS, Gilles, ELENA, Joanne w., WRENSCH, Margaret, SAVAGE, Sharon a., SILVERMAN, Debra t., WENTZENSEN, Nicolas, GILES, Graham g., ANDRULIS, Irene l., AMOS, Christopher i., COTTERCHIO, Michelle, TANG, Ze-zhong, SIERRASESÚMAGA, Luis, VISVANATHAN, Kala, CONSONNI, Dario, KURTZ, Robert c., ALBANES, Demetrius, BURDETT, Laurie, TRICHOPOULOS, Dimitrios, TJØNNELAND, Anne, OLSON, Sara h., CHOW, Wong-ho, JOHNSON, Alison, KROGH, Vittorio, BUENO DE MESQUITA, H. bas, BUTLER, Mary a., BEANE FREEMAN, Laura, WHITE, Emily, KRATZ, Christian p., GRAUBARD, Barry i., HOLLY, Elizabeth a., BLOT, William j., ARSLAN, Alan a., HALLMANS, Göran, FUCHS, Charles s., TOBIAS, Geoffrey s., SAMPSON, Joshua, PETERS, Ulrike, DUELL, Eric j., BRINTON, Louise a., JENAB, Mazda, YU, Herbert, HOOVER, Robert n., KOVAKS, Joseph, CAPORASO, Neil e., LISSOWSKA, Jolanta, MARENNE, Gaelle, MOORE, Lee e., MENDELSOHN, Julie b., MARCHAND, Loïc le, PÉREZ JURADO, Luis a., PETERSEN, Gloria m., ROTHMAN, Nathaniel, CHUNG, Charles c., MCWILLIAMS, Robert r., KOVAKS, Joseph, RAJARAMAN, Preetha, AMUNDADOTTIR, Laufey, ROTUNNO, Melissa, CARREON, Tania, CHATTERJEE, Nilanjan, BERG, Christine d., GOLDIN, Lynn r., INSKIP, Peter d., BARKAUSKAS, Donald a., DEAN, Michael c., FEYCHTING, Maria, TAYLOR, Philip r., WU, Xifeng, ANDERSSON, Ulrika, VIRTAMO, Jarmo, GILLANDERS, Elizabeth m., MALATS, Núria, DAVIS, Faith g., BLACK, Amanda, HAIMAN, Christopher a., DEAN, Michael c., MELIN, Beatrice s., GOLDSTEIN, Alisa m., HUNTER, David j., FREEDMAN, Neal d., LIAO, Linda, BOUTRON-RUAULT, Marie-christine, HOFFMAN BOLTON, Judith a., BERNDT, Sonja i., RYBICKI, Benjamin a., LACROIX, Andrea, RABE, Kari g., HANKINSON, Susan e., BARIS, Dalsu, FIGUEROA, Jonine d., BRACCI, Paige m., SEVERI, Gianluca, MCKEAN-COWDIN, Roberta, KOH, Woon-puay, WEINSTEIN, Stephanie j., MANDELSON, Margaret t., GAO, Yu-tang, SPITZ, Margaret r., SCHWARTZ, Ann g., YU, Kai, KOLONEL, Laurence n., HARTGE, Patricia, HARRIS, Curtis c., TERAS, Lauren r., BURING, Julie e., FRAUMENI JR., Joseph f., MCGLYNN, Katherine a., YUAN, Jian-min, GREENE, Mark h., SESSO, Howard d., RIBOLI, Elio, MIRABELLO, Lisa, SCHWARTZ, Kendra l., JIAO, Li, RISCH, Harvey a., WOLK, Alicja, HSING, Ann w., ABNET, Christian c., MCNEILL, Lorna h., PROKUNINA-OLSSON, Ludmila, WOLPIN, Brian m., GARCIA CLOSAS, Montserrat, MICHAUD, Dominique s., GAZIANO, J. michael m., LI, Donghui, JOHANSEN, Christoffer, ZIEGLER, Regina g., STEVENS, Victoria l.. Detectable clonal mosaicism and its relationship to aging and cancer. _Nature Genetics_. 2012. Vol. 44, núm. 6, pàgs. 651-U68. [consulta: 11 de abril de 2026]. [Disponible a: https://hdl.handle.net/2445/126522]