The origin and evolution of mutations in acute myeloid leukemia

John S. Welch; 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

doi:10.1016/j.cell.2012.06.023

The origin and evolution of mutations in acute myeloid leukemia

John S. Welch, 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 LuQunyuan 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

Bioinformatics & Computational Biology

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1257 Scopus citations

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.

Original language	English (US)
Pages (from-to)	264-278
Number of pages	15
Journal	Cell
Volume	150
Issue number	2
DOIs	https://doi.org/10.1016/j.cell.2012.06.023
State	Published - Jul 20 2012

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

MD Anderson CCSG core facilities

Bioinformatics Shared Resource

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10.1016/j.cell.2012.06.023

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Welch, J. S., Ley, T. J., Link, D. C., Miller, C. A., Larson, D. E., Koboldt, D. C., Wartman, L. D., Lamprecht, T. L., Liu, F., Xia, J., Kandoth, C., Fulton, R. S., McLellan, M. D., Dooling, D. J., Wallis, J. W., Chen, K., Harris, C. C., Schmidt, H. K., Kalicki-Veizer, J. M., ... Wilson, R. K. (2012). The origin and evolution of mutations in acute myeloid leukemia. Cell, 150(2), 264-278. https://doi.org/10.1016/j.cell.2012.06.023

Welch, JS, Ley, TJ, Link, DC, Miller, CA, Larson, DE, Koboldt, DC, Wartman, LD, Lamprecht, TL, Liu, F, Xia, J, Kandoth, C, Fulton, RS, McLellan, MD, Dooling, DJ, Wallis, JW, Chen, K, Harris, CC, Schmidt, HK, Kalicki-Veizer, JM, Lu, C, Zhang, Q, Lin, L, O'Laughlin, MD, McMichael, JF, Delehaunty, KD, Fulton, LA, Magrini, VJ, McGrath, SD, Demeter, RT, Vickery, TL, Hundal, J, Cook, LL, Swift, GW, Reed, JP, Alldredge, PA, Wylie, TN, Walker, JR, Watson, MA, Heath, SE, Shannon, WD, Varghese, N, Nagarajan, R, Payton, JE, Baty, JD, Kulkarni, S, Klco, JM, Tomasson, MH, Westervelt, P, Walter, MJ, Graubert, TA, Dipersio, JF, Ding, L, Mardis, ER & Wilson, RK 2012, 'The origin and evolution of mutations in acute myeloid leukemia', Cell, vol. 150, no. 2, pp. 264-278. https://doi.org/10.1016/j.cell.2012.06.023

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title = "The origin and evolution of mutations in acute myeloid leukemia",

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.",

author = "Welch, {John S.} and Ley, {Timothy J.} and Link, {Daniel C.} and Miller, {Christopher A.} and Larson, {David E.} and Koboldt, {Daniel C.} and Wartman, {Lukas D.} and Lamprecht, {Tamara L.} and Fulu Liu and Jun Xia and Cyriac Kandoth and Fulton, {Robert S.} and McLellan, {Michael D.} and Dooling, {David J.} and Wallis, {John W.} and Ken Chen and Harris, {Christopher C.} and Schmidt, {Heather K.} and Kalicki-Veizer, {Joelle M.} and Charles Lu and Qunyuan Zhang and Ling Lin and O'Laughlin, {Michelle D.} and McMichael, {Joshua F.} and Delehaunty, {Kim D.} and Fulton, {Lucinda A.} and Magrini, {Vincent J.} and McGrath, {Sean D.} and Demeter, {Ryan T.} and Vickery, {Tammi L.} and Jasreet Hundal and Cook, {Lisa L.} and Swift, {Gary W.} and Reed, {Jerry P.} and Alldredge, {Patricia A.} and Wylie, {Todd N.} and Walker, {Jason R.} and Watson, {Mark A.} and Heath, {Sharon E.} and Shannon, {William D.} and Nobish Varghese and Rakesh Nagarajan and Payton, {Jacqueline E.} and Baty, {Jack D.} and Shashikant Kulkarni and Klco, {Jeffery M.} and Tomasson, {Michael H.} and Peter Westervelt and Walter, {Matthew J.} and Graubert, {Timothy A.} and Dipersio, {John F.} and Li Ding and Mardis, {Elaine R.} and Wilson, {Richard K.}",

year = "2012",

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doi = "10.1016/j.cell.2012.06.023",

language = "English (US)",

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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.

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The origin and evolution of mutations in acute myeloid leukemia

Abstract

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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