Original Article

Leukemia advance online publication 18 April 2017; doi: 10.1038/leu.2017.86

The mutational oncoprint of recurrent cytogenetic abnormalities in adult patients with de novo acute myeloid leukemia

A-K Eisfeld1,9, K Mrózek1,9, J Kohlschmidt1,2, D Nicolet1,2, S Orwick3, C J Walker1, K W Kroll3, J S Blachly3, A J Carroll4, J E Kolitz5, B L Powell6, E S Wang7, R M Stone8, A de la Chapelle1, J C Byrd3,10 and C D Bloomfield1,10

  1. 1The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA
  2. 2Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN, USA
  3. 3Division of Hematology, Department of Internal Medicine, The Ohio State University, Comprehensive Cancer Center, Columbus, OH, USA
  4. 4Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA
  5. 5Monter Cancer Center, Hofstra North Shore-Long Island Jewish School of Medicine, Lake Success, NY, USA
  6. 6Comprehensive Cancer Center of Wake Forest University, Winston-Salem, NC, USA
  7. 7Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA
  8. 8Department of Medical Oncology, Dana-Farber/Partners CancerCare, Boston, MA, USA

Correspondence: Dr A-K Eisfeld, The Ohio State University Comprehensive Cancer Center, 460 West 12th Avenue, Room 850, Columbus, OH 43210-1228, USA E-mail: ann-kathrin.eisfeld@osumc.edu; Dr K Mrózek, The Ohio State University Comprehensive Cancer Center, 370A Tzagournis Medical Research Facility, 420 West 12th Avenue, Columbus, OH 43210-1228, USA E-mail: krzysztof.mrozek@osumc.edu; Professor CD Bloomfield, The Ohio State University Comprehensive Cancer Center, C933 James Cancer Hospital, 460 West 10th Avenue, Columbus, OH 43210-1228, USA. E-mail: clara.bloomfield@osumc.edu

9These authors contributed equally to this work.

10These senior authors contributed equally to this work.

Received 2 November 2016; Revised 17 January 2017; Accepted 16 February 2017
Accepted article preview online 24 March 2017; Advance online publication 18 April 2017

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Abstract

Recurrent chromosomal abnormalities and gene mutations detected at the time of diagnosis of acute myeloid leukemia (AML) are associated with particular disease features, treatment response and survival of AML patients, and are used to denote specific disease entities in the World Health Organization classification of myeloid neoplasms and acute leukemia. However, large studies that integrate cytogenetic and comprehensive mutational information are scarce. We created a comprehensive oncoprint of mutations associated with recurrent cytogenetic findings by combining the information on mutational patterns of 80 cancer- and leukemia-associated genes with cytogenetic findings in 1603 adult patients with de novo AML. We show unique differences in the mutational profiles among major cytogenetic subsets, identify novel associations between recurrent cytogenetic abnormalities and both specific gene mutations and gene functional groups, and reveal differences in cytogenetic and mutational features between patients younger than 60 years and those aged 60 years or older. The identified associations between cytogenetic and molecular genetic data may help guide mutation testing in AML, and result in more focused application of targeted therapy in patients with de novo AML.