TY - JOUR
T1 - The origin and evolution of mutations in acute myeloid leukemia
AU - Welch, John S.
AU - Ley, Timothy J.
AU - Link, Daniel C.
AU - Miller, Christopher A.
AU - Larson, David E.
AU - Koboldt, Daniel C.
AU - Wartman, Lukas D.
AU - Lamprecht, Tamara L.
AU - Liu, Fulu
AU - Xia, Jun
AU - Kandoth, Cyriac
AU - Fulton, Robert S.
AU - McLellan, Michael D.
AU - Dooling, David J.
AU - Wallis, John W.
AU - Chen, Ken
AU - Harris, Christopher C.
AU - Schmidt, Heather K.
AU - Kalicki-Veizer, Joelle M.
AU - Lu, Charles
AU - Zhang, Qunyuan
AU - Lin, Ling
AU - O'Laughlin, Michelle D.
AU - McMichael, Joshua F.
AU - Delehaunty, Kim D.
AU - Fulton, Lucinda A.
AU - Magrini, Vincent J.
AU - McGrath, Sean D.
AU - Demeter, Ryan T.
AU - Vickery, Tammi L.
AU - Hundal, Jasreet
AU - Cook, Lisa L.
AU - Swift, Gary W.
AU - Reed, Jerry P.
AU - Alldredge, Patricia A.
AU - Wylie, Todd N.
AU - Walker, Jason R.
AU - Watson, Mark A.
AU - Heath, Sharon E.
AU - Shannon, William D.
AU - Varghese, Nobish
AU - Nagarajan, Rakesh
AU - Payton, Jacqueline E.
AU - Baty, Jack D.
AU - Kulkarni, Shashikant
AU - Klco, Jeffery M.
AU - Tomasson, Michael H.
AU - Westervelt, Peter
AU - Walter, Matthew J.
AU - Graubert, Timothy A.
AU - Dipersio, John F.
AU - Ding, Li
AU - Mardis, Elaine R.
AU - Wilson, Richard K.
PY - 2012/7/20
Y1 - 2012/7/20
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84864255882&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2012.06.023
DO - 10.1016/j.cell.2012.06.023
M3 - Article
C2 - 22817890
AN - SCOPUS:84864255882
SN - 0092-8674
VL - 150
SP - 264
EP - 278
JO - Cell
JF - Cell
IS - 2
ER -