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

Research output: Contribution to journalArticlepeer-review

1054 Scopus citations


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 languageEnglish
Pages (from-to)66-72
Number of pages7
Issue number7218
StatePublished - Nov 6 2008


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