| Literature DB >> 22817890 |
John S Welch1, Timothy J Ley, Daniel C Link, Christopher A Miller, David E Larson, Daniel C Koboldt, Lukas D Wartman, Tamara L Lamprecht, Fulu Liu, Jun Xia, Cyriac Kandoth, Robert S Fulton, Michael D McLellan, David J Dooling, John W Wallis, Ken Chen, Christopher C Harris, Heather K Schmidt, Joelle M Kalicki-Veizer, Charles Lu, Qunyuan Zhang, Ling Lin, Michelle D O'Laughlin, Joshua F McMichael, Kim D Delehaunty, Lucinda A Fulton, Vincent J Magrini, Sean D McGrath, Ryan T Demeter, Tammi L Vickery, Jasreet Hundal, Lisa L Cook, Gary W Swift, Jerry P Reed, Patricia A Alldredge, Todd N Wylie, Jason R Walker, Mark A Watson, Sharon E Heath, William D Shannon, Nobish Varghese, Rakesh Nagarajan, Jacqueline E Payton, Jack D Baty, Shashikant Kulkarni, Jeffery M Klco, Michael H Tomasson, Peter Westervelt, Matthew J Walter, Timothy A Graubert, John F DiPersio, Li Ding, Elaine R Mardis, Richard K Wilson.
Abstract
Most mutations in cancer genomes are thought to be acquired after the initiating event, which may cause genomic instability and drive clonal evolution. However, for acute myeloid leukemia (AML), normal karyotypes are common, and genomic instability is unusual. To better understand clonal evolution in AML, we sequenced the genomes of M3-AML samples with a known initiating event (PML-RARA) versus the genomes of normal karyotype M1-AML samples and the exomes of hematopoietic stem/progenitor cells (HSPCs) from healthy people. Collectively, the data suggest that most of the mutations found in AML genomes are actually random events that occurred in HSPCs before they acquired the initiating mutation; the mutational history of that cell is "captured" as the clone expands. In many cases, only one or two additional, cooperating mutations are needed to generate the malignant founding clone. Cells from the founding clone can acquire additional cooperating mutations, yielding subclones that can contribute to disease progression and/or relapse.Entities:
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Year: 2012 PMID： 22817890 PMCID： PMC3407563 DOI： 10.1016/j.cell.2012.06.023
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582