DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome

Timothy J. Ley; Elaine R. Mardis; Li Ding; Bob Fulton; Michael D. McLellan; Ken Chen; David Dooling; Brian H. Dunford-Shore; Sean McGrath; Matthew Hickenbotham; Lisa Cook; Rachel Abbott; David E. Larson; Dan C. Koboldt; Craig Pohl; Scott Smith; Amy Hawkins; Scott Abbott; Devin Locke; Ladeana W. Hillier; Tracie Miner; Lucinda Fulton; Vincent Magrini; Todd Wylie; Jarret Glasscock; Joshua Conyers; Nathan Sander; Xiaoqi Shi; John R. Osborne; Patrick Minx; David Gordon; Asif Chinwalla; Yu Zhao; Rhonda E. Ries; Jacqueline E. Payton; Peter Westervelt; Michael H. Tomasson; Mark Watson; Jack Baty; Jennifer Ivanovich; Sharon Heath; William D. Shannon; Rakesh Nagarajan; Matthew J. Walter; Daniel C. Link; Timothy A. Graubert; John F. DiPersio; Richard K. Wilson

doi:10.1038/nature07485

DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome

Timothy J. Ley, Elaine R. Mardis, Li Ding, Bob Fulton, Michael D. McLellan, Ken Chen, David Dooling, Brian H. Dunford-Shore, Sean McGrath, Matthew Hickenbotham, Lisa Cook, Rachel Abbott, David E. Larson, Dan C. Koboldt, Craig Pohl, Scott Smith, Amy Hawkins, Scott Abbott, Devin Locke, Ladeana W. HillierTracie Miner, Lucinda Fulton, Vincent Magrini, Todd Wylie, Jarret Glasscock, Joshua Conyers, Nathan Sander, Xiaoqi Shi, John R. Osborne, Patrick Minx, David Gordon, Asif Chinwalla, Yu Zhao, Rhonda E. Ries, Jacqueline E. Payton, Peter Westervelt, Michael H. Tomasson, Mark Watson, Jack Baty, Jennifer Ivanovich, Sharon Heath, William D. Shannon, Rakesh Nagarajan, Matthew J. Walter, Daniel C. Link, Timothy A. Graubert, John F. DiPersio, Richard K. Wilson

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Abstract

Acute myeloid leukaemia is a highly malignant haematopoietic tumour that affects about 13,000 adults in the United States each year. The treatment of this disease has changed little in the past two decades, because most of the genetic events that initiate the disease remain undiscovered. Whole-genome sequencing is now possible at a reasonable cost and timeframe to use this approach for the unbiased discovery of tumour-specific somatic mutations that alter the protein-coding genes. Here we present the results obtained from sequencing a typical acute myeloid leukaemia genome, and its matched normal counterpart obtained from the same patient's skin. We discovered ten genes with acquired mutations; two were previously described mutations that are thought to contribute to tumour progression, and eight were new mutations present in virtually all tumour cells at presentation and relapse, the function of which is not yet known. Our study establishes whole-genome sequencing as an unbiased method for discovering cancer-initiating mutations in previously unidentified genes that may respond to targeted therapies.

Original language	English (US)
Pages (from-to)	66-72
Number of pages	7
Journal	Nature
Volume	456
Issue number	7218
DOIs	https://doi.org/10.1038/nature07485
State	Published - Nov 6 2008
Externally published	Yes

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Ley, T. J., Mardis, E. R., Ding, L., Fulton, B., McLellan, M. D., Chen, K., Dooling, D., Dunford-Shore, B. H., McGrath, S., Hickenbotham, M., Cook, L., Abbott, R., Larson, D. E., Koboldt, D. C., Pohl, C., Smith, S., Hawkins, A., Abbott, S., Locke, D., ... Wilson, R. K. (2008). DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome. Nature, 456(7218), 66-72. https://doi.org/10.1038/nature07485

Ley, TJ, Mardis, ER, Ding, L, Fulton, B, McLellan, MD, Chen, K, Dooling, D, Dunford-Shore, BH, McGrath, S, Hickenbotham, M, Cook, L, Abbott, R, Larson, DE, Koboldt, DC, Pohl, C, Smith, S, Hawkins, A, Abbott, S, Locke, D, Hillier, LW, Miner, T, Fulton, L, Magrini, V, Wylie, T, Glasscock, J, Conyers, J, Sander, N, Shi, X, Osborne, JR, Minx, P, Gordon, D, Chinwalla, A, Zhao, Y, Ries, RE, Payton, JE, Westervelt, P, Tomasson, MH, Watson, M, Baty, J, Ivanovich, J, Heath, S, Shannon, WD, Nagarajan, R, Walter, MJ, Link, DC, Graubert, TA, DiPersio, JF & Wilson, RK 2008, 'DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome', Nature, vol. 456, no. 7218, pp. 66-72. https://doi.org/10.1038/nature07485

@article{714da8bbbc6043428817e134d445aac4,

title = "DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome",

abstract = "Acute myeloid leukaemia is a highly malignant haematopoietic tumour that affects about 13,000 adults in the United States each year. The treatment of this disease has changed little in the past two decades, because most of the genetic events that initiate the disease remain undiscovered. Whole-genome sequencing is now possible at a reasonable cost and timeframe to use this approach for the unbiased discovery of tumour-specific somatic mutations that alter the protein-coding genes. Here we present the results obtained from sequencing a typical acute myeloid leukaemia genome, and its matched normal counterpart obtained from the same patient's skin. We discovered ten genes with acquired mutations; two were previously described mutations that are thought to contribute to tumour progression, and eight were new mutations present in virtually all tumour cells at presentation and relapse, the function of which is not yet known. Our study establishes whole-genome sequencing as an unbiased method for discovering cancer-initiating mutations in previously unidentified genes that may respond to targeted therapies.",

author = "Ley, {Timothy J.} and Mardis, {Elaine R.} and Li Ding and Bob Fulton and McLellan, {Michael D.} and Ken Chen and David Dooling and Dunford-Shore, {Brian H.} and Sean McGrath and Matthew Hickenbotham and Lisa Cook and Rachel Abbott and Larson, {David E.} and Koboldt, {Dan C.} and Craig Pohl and Scott Smith and Amy Hawkins and Scott Abbott and Devin Locke and Hillier, {Ladeana W.} and Tracie Miner and Lucinda Fulton and Vincent Magrini and Todd Wylie and Jarret Glasscock and Joshua Conyers and Nathan Sander and Xiaoqi Shi and Osborne, {John R.} and Patrick Minx and David Gordon and Asif Chinwalla and Yu Zhao and Ries, {Rhonda E.} and Payton, {Jacqueline E.} and Peter Westervelt and Tomasson, {Michael H.} and Mark Watson and Jack Baty and Jennifer Ivanovich and Sharon Heath and Shannon, {William D.} and Rakesh Nagarajan and Walter, {Matthew J.} and Link, {Daniel C.} and Graubert, {Timothy A.} and DiPersio, {John F.} and Wilson, {Richard K.}",

note = "Funding Information: Acknowledgements We are grateful to our AML patients and their families, and to A. J. Siteman, whose generous and visionary gift provided the main funding source for this study. We thank G. Flance, D. Kipnis and K. Polonsky for their support, and C. Bloomfield, M. Caligiuri and J. Vardiman from the Cancer and Leukemia Group B for providing important AML samples for validation studies. We also thank the staff of The Genome Center at Washington University for their support of and their many contributions to this project, and H. Li of the Sanger Institute for assistance with the use of Maq. Further funding was provided by the National Cancer Institute (T.J.L.), the National Human Genome Research Institute (R.K.W.), and the Barnes-Jewish Hospital Foundation (T.J.L.).",

year = "2008",

month = nov,

day = "6",

doi = "10.1038/nature07485",

language = "English (US)",

volume = "456",

pages = "66--72",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Publishing Group",

number = "7218",

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TY - JOUR

T1 - DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome

AU - Ley, Timothy J.

AU - Mardis, Elaine R.

AU - Ding, Li

AU - Fulton, Bob

AU - McLellan, Michael D.

AU - Chen, Ken

AU - Dooling, David

AU - Dunford-Shore, Brian H.

AU - McGrath, Sean

AU - Hickenbotham, Matthew

AU - Cook, Lisa

AU - Abbott, Rachel

AU - Larson, David E.

AU - Koboldt, Dan C.

AU - Pohl, Craig

AU - Smith, Scott

AU - Hawkins, Amy

AU - Abbott, Scott

AU - Locke, Devin

AU - Hillier, Ladeana W.

AU - Miner, Tracie

AU - Fulton, Lucinda

AU - Magrini, Vincent

AU - Wylie, Todd

AU - Glasscock, Jarret

AU - Conyers, Joshua

AU - Sander, Nathan

AU - Shi, Xiaoqi

AU - Osborne, John R.

AU - Minx, Patrick

AU - Gordon, David

AU - Chinwalla, Asif

AU - Zhao, Yu

AU - Ries, Rhonda E.

AU - Payton, Jacqueline E.

AU - Westervelt, Peter

AU - Tomasson, Michael H.

AU - Watson, Mark

AU - Baty, Jack

AU - Ivanovich, Jennifer

AU - Heath, Sharon

AU - Shannon, William D.

AU - Nagarajan, Rakesh

AU - Walter, Matthew J.

AU - Link, Daniel C.

AU - Graubert, Timothy A.

AU - DiPersio, John F.

AU - Wilson, Richard K.

N1 - Funding Information: Acknowledgements We are grateful to our AML patients and their families, and to A. J. Siteman, whose generous and visionary gift provided the main funding source for this study. We thank G. Flance, D. Kipnis and K. Polonsky for their support, and C. Bloomfield, M. Caligiuri and J. Vardiman from the Cancer and Leukemia Group B for providing important AML samples for validation studies. We also thank the staff of The Genome Center at Washington University for their support of and their many contributions to this project, and H. Li of the Sanger Institute for assistance with the use of Maq. Further funding was provided by the National Cancer Institute (T.J.L.), the National Human Genome Research Institute (R.K.W.), and the Barnes-Jewish Hospital Foundation (T.J.L.).

PY - 2008/11/6

Y1 - 2008/11/6

N2 - Acute myeloid leukaemia is a highly malignant haematopoietic tumour that affects about 13,000 adults in the United States each year. The treatment of this disease has changed little in the past two decades, because most of the genetic events that initiate the disease remain undiscovered. Whole-genome sequencing is now possible at a reasonable cost and timeframe to use this approach for the unbiased discovery of tumour-specific somatic mutations that alter the protein-coding genes. Here we present the results obtained from sequencing a typical acute myeloid leukaemia genome, and its matched normal counterpart obtained from the same patient's skin. We discovered ten genes with acquired mutations; two were previously described mutations that are thought to contribute to tumour progression, and eight were new mutations present in virtually all tumour cells at presentation and relapse, the function of which is not yet known. Our study establishes whole-genome sequencing as an unbiased method for discovering cancer-initiating mutations in previously unidentified genes that may respond to targeted therapies.

AB - Acute myeloid leukaemia is a highly malignant haematopoietic tumour that affects about 13,000 adults in the United States each year. The treatment of this disease has changed little in the past two decades, because most of the genetic events that initiate the disease remain undiscovered. Whole-genome sequencing is now possible at a reasonable cost and timeframe to use this approach for the unbiased discovery of tumour-specific somatic mutations that alter the protein-coding genes. Here we present the results obtained from sequencing a typical acute myeloid leukaemia genome, and its matched normal counterpart obtained from the same patient's skin. We discovered ten genes with acquired mutations; two were previously described mutations that are thought to contribute to tumour progression, and eight were new mutations present in virtually all tumour cells at presentation and relapse, the function of which is not yet known. Our study establishes whole-genome sequencing as an unbiased method for discovering cancer-initiating mutations in previously unidentified genes that may respond to targeted therapies.

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U2 - 10.1038/nature07485

DO - 10.1038/nature07485

M3 - Article

C2 - 18987736

AN - SCOPUS:55549101623

SN - 0028-0836

VL - 456

SP - 66

EP - 72

JO - Nature

JF - Nature

IS - 7218

ER -

DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome

Abstract

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