Recurring Mutations Found by Sequencing an Acute Myeloid Leukemia Genome

Elaine R MARDIS; Michael H TOMASSON; Li Ding; Lucinda A FULTON; Devin P LOCKE; Vincent J MAGRINI; Rachel M ABBOTT; Tammi L VICKERY; Jerry S REED; Jody S ROBINSON; Todd WYLIE; Scott M SMITH; Lynn CARMICHAEL; David J DOOLING; James M ELDRED; Christopher C HARRIS; Jason WALKER; Joshua B PECK; FEIYU DU; Adam F DUKES; Gabriel E SANDERSON; Anthony M BRUMMETT; Joshua F MCMICHAEL; Eric CLARK; David E LARSON; Rick J MEYER; Jonathan K SCHINDLER; Craig S POHL; John W WALLIS; XIAOQI SHI; LING LIN; Heather SCHMIDT; YUZHU TANG; Carrie HAIPEK; Madeline E WIECHERT; Michael D MCLELLAN; Jolynda V IVY; Joelle KALICKI; Glendoria ELLIOTT; Jacqueline E PAYTON; Rhonda E RIES; Peter WESTERVELT; Mark A WATSON; Jack BATY; Sharon HEATH; KEN CHEN; William D SHANNON; Rakesh NAGARAJAN; Daniel C LINK; Matthew J Walter; Timothy A GRAUBERT; John F DIPERSIO; Richard K WILSON; Timothy J LEY; Daniel C KOBOLDT; Robert S FULTON; Kim D DELEHAUNTY; Sean D MCGRATH

doi:10.1056/NEJMoa0903840

Back

Recurring Mutations Found by Sequencing an Acute Myeloid Leukemia Genome

Journal article

Open access

Peer reviewed

Recurring Mutations Found by Sequencing an Acute Myeloid Leukemia Genome

Elaine R MARDIS, Michael H TOMASSON, Li Ding, Lucinda A FULTON, Devin P LOCKE, Vincent J MAGRINI, Rachel M ABBOTT, Tammi L VICKERY, Jerry S REED, Jody S ROBINSON, …

The New England journal of medicine, Vol.361(11), pp.1058-1066

2009

DOI: 10.1056/NEJMoa0903840

PMCID: PMC3201812

PMID: 19657110

Files and links (1)

url

https://doi.org/10.1056/NEJMoa0903840View

Published (Version of record) Open Access

Abstract

BACKGROUND The full complement of DNA mutations that are responsible for the pathogenesis of acute myeloid leukemia (AML) is not yet known. METHODS We used massively parallel DNA sequencing to obtain a very high level of coverage (approximately 98%) of a primary, cytogenetically normal, de novo genome for AML with minimal maturation (AML-M1) and a matched normal skin genome. RESULTS We identified 12 acquired (somatic) mutations within the coding sequences of genes and 52 somatic point mutations in conserved or regulatory portions of the genome. All mutations appeared to be heterozygous and present in nearly all cells in the tumor sample. Four of the 64 mutations occurred in at least 1 additional AML sample in 188 samples that were tested. Mutations in NRAS and NPM1 had been identified previously in patients with AML, but two other mutations had not been identified. One of these mutations, in the IDH1 gene, was present in 15 of 187 additional AML genomes tested and was strongly associated with normal cytogenetic status; it was present in 13 of 80 cytogenetically normal samples (16%). The other was a nongenic mutation in a genomic region with regulatory potential and conservation in higher mammals; we detected it in one additional AML tumor. The AML genome that we sequenced contains approximately 750 point mutations, of which only a small fraction are likely to be relevant to pathogenesis.

Hematologic and hematopoietic diseases

Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis

Biological and medical sciences

General aspects

Medical sciences

Details

Title: Subtitle: Recurring Mutations Found by Sequencing an Acute Myeloid Leukemia Genome
Creators: Elaine R MARDIS - Department of Genetics, Washington University, St. Louis, United States
Michael H TOMASSON - Department of Medicine, Washington University, St. Louis, United States
Li Ding - Department of Genetics, Washington University, St. Louis, United States
Lucinda A FULTON - Genome Center, Washington University, St. Louis, United States
Devin P LOCKE - Genome Center, Washington University, St. Louis, United States
Vincent J MAGRINI - Department of Genetics, Washington University, St. Louis, United States
Rachel M ABBOTT - Genome Center, Washington University, St. Louis, United States
Tammi L VICKERY - Genome Center, Washington University, St. Louis, United States
Jerry S REED - Genome Center, Washington University, St. Louis, United States
Jody S ROBINSON - Genome Center, Washington University, St. Louis, United States
Todd WYLIE - Genome Center, Washington University, St. Louis, United States
Scott M SMITH - Genome Center, Washington University, St. Louis, United States
Lynn CARMICHAEL - Genome Center, Washington University, St. Louis, United States
David J DOOLING - Genome Center, Washington University, St. Louis, United States
James M ELDRED - Department of Genetics, Washington University, St. Louis, United States
Christopher C HARRIS - Department of Genetics, Washington University, St. Louis, United States
Jason WALKER - Department of Genetics, Washington University, St. Louis, United States
Joshua B PECK - Department of Genetics, Washington University, St. Louis, United States
FEIYU DU - Department of Genetics, Washington University, St. Louis, United States
Adam F DUKES - Department of Genetics, Washington University, St. Louis, United States
Gabriel E SANDERSON - Department of Genetics, Washington University, St. Louis, United States
Anthony M BRUMMETT - Department of Genetics, Washington University, St. Louis, United States
Joshua F MCMICHAEL - Department of Genetics, Washington University, St. Louis, United States
Eric CLARK - Department of Genetics, Washington University, St. Louis, United States
David E LARSON - Genome Center, Washington University, St. Louis, United States
Rick J MEYER - Department of Genetics, Washington University, St. Louis, United States
Jonathan K SCHINDLER - Department of Genetics, Washington University, St. Louis, United States
Craig S POHL - Department of Genetics, Washington University, St. Louis, United States
John W WALLIS - Department of Genetics, Washington University, St. Louis, United States
XIAOQI SHI - Department of Genetics, Washington University, St. Louis, United States
LING LIN - Department of Genetics, Washington University, St. Louis, United States
Heather SCHMIDT - Department of Genetics, Washington University, St. Louis, United States
YUZHU TANG - Department of Genetics, Washington University, St. Louis, United States
Carrie HAIPEK - Department of Genetics, Washington University, St. Louis, United States
Madeline E WIECHERT - Department of Genetics, Washington University, St. Louis, United States
Michael D MCLELLAN - Genome Center, Washington University, St. Louis, United States
Jolynda V IVY - Department of Genetics, Washington University, St. Louis, United States
Joelle KALICKI - Department of Genetics, Washington University, St. Louis, United States
Glendoria ELLIOTT - Department of Genetics, Washington University, St. Louis, United States
Jacqueline E PAYTON - Department of Pathology and Immunology, Washington University, St. Louis, United States
Rhonda E RIES - Department of Medicine, Washington University, St. Louis, United States
Peter WESTERVELT - Department of Medicine, Washington University, St. Louis, United States
Mark A WATSON - Department of Pathology and Immunology, Washington University, St. Louis, United States
Jack BATY - Division of Biostatistics, Washington University, St. Louis, United States
Sharon HEATH - Department of Medicine, Washington University, St. Louis, United States
KEN CHEN - Genome Center, Washington University, St. Louis, United States
William D SHANNON - Department of Medicine, Washington University, St. Louis, United States
Rakesh NAGARAJAN - Department of Pathology and Immunology, Washington University, St. Louis, United States
Daniel C LINK - Department of Medicine, Washington University, St. Louis, United States
Matthew J Walter - Department of Medicine, Washington University, St. Louis, United States
Timothy A GRAUBERT - Department of Medicine, Washington University, St. Louis, United States
John F DIPERSIO - Department of Medicine, Washington University, St. Louis, United States
Richard K WILSON - Department of Genetics, Washington University, St. Louis, United States
Timothy J LEY - Department of Genetics, Washington University, St. Louis, United States
Daniel C KOBOLDT - Genome Center, Washington University, St. Louis, United States
Robert S FULTON - Genome Center, Washington University, St. Louis, United States
Kim D DELEHAUNTY - Genome Center, Washington University, St. Louis, United States
Sean D MCGRATH - Genome Center, Washington University, St. Louis, United States
Resource Type: Journal article
Publication Details: The New England journal of medicine, Vol.361(11), pp.1058-1066
Publisher: Massachusetts Medical Society
DOI: 10.1056/NEJMoa0903840
PMID: 19657110
PMCID: PMC3201812
ISSN: 0028-4793
eISSN: 1533-4406
Language: English
Date published: 2009
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9984094216302771

Metrics

9 Record Views

1815 Times Cited - Web of Science

See more details