@article{597b1cca3ce44a2ab03d9b2247830cad,
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",
volume = "456",
pages = "66--72",
journal = "Nature",
issn = "0028-0836",
number = "7218",
}