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Genomic and Epigenomic Landscapes of Adult De Novo Acute Myeloid Leukemia
Open accessAbstract
BACKGROUND: Many mutations that contribute to the pathogenesis of acute myeloid leukemia (AML) are undefined. The relationships between patterns of mutations and epigenetic phenotypes are not yet clear. METHODS: We analyzed the genomes of 200 clinically annotated adult cases of de novo AML, using either whole-genome sequencing (50 cases) or whole-exome sequencing (150 cases), along with RNA and microRNA sequencing and DNA-methylation analysis. RESULTS: AML genomes have fewer mutations than most other adult cancers, with an average of only 13 mutations found in genes. Of these, an average of 5 are in genes that are recurrently mutated in AML. A total of 23 genes were significantly mutated, and another 237 were mutated in two or more samples. Nearly all samples had at least 1 nonsynonymous mutation in one of nine categories of genes that are almost certainly relevant for pathogenesis, including transcription-factor fusions (18% of cases), the gene encoding nucleophosmin (NPM1) (27%), tumor-suppressor genes (16%), DNA-methylation-related genes (44%), signaling genes (59%), chromatin-modifying genes (30%), myeloid transcription-factor genes (22%), cohesin-complex genes (13%), and spliceosome-complex genes (14%). Patterns of cooperation and mutual exclusivity suggested strong biologic relationships among several of the genes and categories. CONCLUSIONS: We identified at least one potential driver mutation in nearly all AML samples and found that a complex interplay of genetic events contributes to AML pathogenesis in individual patients. The databases from this study are widely available to serve as a foundation for further investigations of AML pathogenesis, classification, and risk stratification. (Funded by the National Institutes of Health.).
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“in line with clinical observations of adults and patients with myeloid malignancies typically lacking this oncogene (43).”
From PU.1-Dependent Enhancer Inhibition Separates Tet2 -Deficient Hematopoiesis from Malignant Transformation (2022) · cites this paper as [43]
Experimental — accuracy not yet measuredIn the citing paper
“both TET2 and TET3 are highly expressed in our model and in human AML27 (Supplementary Figure S2d).”
From Vitamin C-induced epigenomic remodelling in IDH1 mutant acute myeloid leukaemia (2018) · cites this paper as [27]
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“But many of the most commonly seen mutations in CHIP are also recurrent drivers of AML 64, myelodysplastic syndrome (MDS) 65–67, myeloproliferative neoplasms 68, and certain lymphomas 69,70.”
From Clonal hematopoiesis in human aging and disease (2019) · cites this paper as [64]
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“Treatment of AML with targeted therapies is particularly promising due to the fact that AMLs have far fewer mutations than most other adult cancers, with an average of only 13 mutations (Mardis et al, 2009; Cancer Genome Atlas Research Network, 2013).”
From Unlocking the potential of retinoic acid in anticancer therapy (2014) · cites this paper as Cancer Genome Atlas Research Network, 2013
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Circos: An information aesthetic for comparative genomicsPreprint
Krzywinski, M. I., Schein, J. E., Birol, İ., Connors, J. M., Gascoyne, R. D., Horsman, D. E., Jones, S. J. M., & Marra, M. A. (2009) · Genome Research · doi:10.1101/gr.092759.109 · Cited by 11,073
Döhner, H., Estey, E. H., Amadori, S., Appelbaum, F. R., Büchner, T., Burnett, A. K., Dombret, H., Fenaux, P., Grimwade, D. J., Larson, R. A., et al. (2009) · Blood · doi:10.1182/blood-2009-07-235358 · Cited by 3,438
MicroRNAs Modulate Hematopoietic Lineage Differentiation
Chen, C.-Z., Li, L., Lodish, H. F., & Bartel, D. P. (2004) · Science · doi:10.1126/science.1091903 · Cited by 3,257
Figueroa, M. E., Abdel-Wahab, O., Lu, C., Ward, P. S., Patel, J., Shih, A., Li, Y., Bhagwat, N., Vasanthakumar, A., Fernandez, H. F., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.11.015 · Cited by 2,766
Massive genomic rearrangement acquired in a single catastrophic event during cancer development
Stephens, P. J., Greenman, C. D., Fu, B., Yang, F., Bignell, G. R., Mudie, L. J., Pleasance, E. D., Lau, K. W., Beare, D., Stebbings, L. A., et al. (2011) · Cell · doi:10.1016/j.cell.2010.11.055 · Cited by 2,414
Recurring mutations found by sequencing an acute myeloid leukemia genome
Mardis, E. R., Ding, L., Dooling, D. J., Larson, D. E., McLellan, M. D., Chen, K., Koboldt, D. C., Fulton, R. S., Delehaunty, K. D., McGrath, S. D., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0903840 · Cited by 2,219
Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing
Ding, L., Ley, T. J., Larson, D. E., Miller, C. A., Koboldt, D. C., Welch, J. S., Ritchey, J. K., Young, M. A., Lamprecht, T., McLellan, M. D., et al. (2012) · Nature · doi:10.1038/nature10738 · Cited by 1,993
Prognostic Relevance of Integrated Genetic Profiling in Acute Myeloid Leukemia
Patel, J. P., Gönen, M., Figueroa, M. E., Fernandez, H. F., Sun, Z., Racevskis, J., Vlierberghe, P. V., Dolgalev, I., Thomas, S., Aminova, O., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1112304 · Cited by 1,990
DNMT3A Mutations in Acute Myeloid Leukemia
Ley, T. J., Ding, L., Walter, M. J., McLellan, M. D., Lamprecht, T., Larson, D. E., Kandoth, C., Payton, J. E., Baty, J., Welch, J., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1005143 · Cited by 1,983
Byrd, J. C. (2002) · Blood · doi:10.1182/blood-2002-03-0772 · Cited by 1,594
The origin and evolution of mutations in acute myeloid leukemia
Welch, J. S., Ley, T. J., Link, D. C., Miller, C. A., Larson, D. E., Koboldt, D. C., Wartman, L. D., Lamprecht, T. L., Liu, F., Xia, J., et al. (2012) · Cell · doi:10.1016/j.cell.2012.06.023 · Cited by 1,575
Saxonov, S., Berg, P., & Brutlag, D. L. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0510310103 · Cited by 1,401
Prognostically Useful Gene-Expression Profiles in Acute Myeloid Leukemia
Valk, P. J. M., Verhaak, R. G. W., Beijen, M. A., Erpelinck, C. A. J., van Doorn-Khosrovani, S. B. V. W., Boer, J. M., Beverloo, H. B., Moorhouse, M. J., van der Spek, P. J., Löwenberg, B., et al. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa040465 · Cited by 1,370
Increased methylation variation in epigenetic domains across cancer types
Hansen, K. D., Timp, W., Bravo, H. C., Sabunciyan, S., Langmead, B., McDonald, O. G., Wen, B., Wu, H., Liu, Y., Diep, D. H., et al. (2011) · Nature Genetics · doi:10.1038/ng.865 · Cited by 1,062
De novo assembly and analysis of RNA-seq data
Robertson, G., Schein, J. E., Chiu, R., Corbett, R., Field, M. A., Jackman, S. D., Mungall, K. L., Lee, S. S., Okada, H. M., Qian, J. Q., et al. (2010) · Nature Methods · doi:10.1038/nmeth.1517 · Cited by 1,028
The role of FLT3 in haematopoietic malignancies
Stirewalt, D. L., & Radich, J. P. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1169 · Cited by 865
Croce, L. D., Raker, V. A., Corsaro, M., Fazi, F., Fanelli, M., Faretta, M., Fuks, F., Lo‐Coco, F., Kouzarides, T., Nervi, C., et al. (2002) · Science · doi:10.1126/science.1065173 · Cited by 786
Rücker, F. G., Schlenk, R. F., Bullinger, L., Käyser, S., Teleanu, V., Kett, H., Habdank, M., Kugler, C.-M., Holzmann, K., Gaidzik, V. I., et al. (2011) · Blood · doi:10.1182/blood-2011-08-375758 · Cited by 694
MuSiC: Identifying mutational significance in cancer genomesPreprint
Dees, N. D., Zhang, Q., Kandoth, C., Wendl, M. C., Schierding, W. S., Koboldt, D. C., Mooney, T. B., Callaway, M. B., Dooling, D. J., Mardis, E. R., et al. (2012) · Genome Research · doi:10.1101/gr.134635.111 · Cited by 686
Cytogenetics in acute leukemia
Mrózek, K., Heerema, N. A., & Bloomfield, C. D. (2003) · Blood Reviews · doi:10.1016/s0268-960x(03)00040-7 · Cited by 672
Dnmt3a-Dependent Nonpromoter DNA Methylation Facilitates Transcription of Neurogenic Genes
Wu, H., Coskun, V., Tao, J., Xie, W., Ge, W., Yoshikawa, K., Li, E., Zhang, Y., & Sun, Y. E. (2010) · Science · doi:10.1126/science.1190485 · Cited by 604
Breems, D. A., van Putten, W. L. J., de Greef, G. E., van Zelderen‐Bhola, S. L., Gerssen‐Schoorl, K. B. J., Mellink, C. H. M., Nieuwint, A. W. M., Jotterand, M., Hagemeijer, A., Beverloo, H. B., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2008.16.0259 · Cited by 576
G ENETICS OF M YELOID L EUKEMIAS
Kelly, L. M., & Gilliland, D. G. (2002) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev.genom.3.032802.115046 · Cited by 541
Corral, J., Lavenir, I., Impey, H. L., Warren, A. J., Forster, A. M., Larson, T., Bell, S. E., McKenzie, A. N. J., King, G., & Rabbitts, T. H. (1996) · Cell · doi:10.1016/s0092-8674(00)81269-6 · Cited by 520
Higuchi, M., O’Brien, D. P., Kumaravelu, P., Lenny, N. T., Yeoh, A. E. J., & Downing, J. R. (2002) · Cancer Cell · doi:10.1016/s1535-6108(02)00016-8 · Cited by 440
Algorithms for Detecting Significantly Mutated Pathways in Cancer
Vandin, F., Upfal, E., & Raphael, B. J. (2011) · Journal of Computational Biology · doi:10.1089/cmb.2010.0265 · Cited by 436
Mrózek, K., Marcucci, G., Nicolet, D., Maharry, K. S., Becker, H., Whitman, S. P., Metzeler, K. H., Schwind, S., Wu, Y.-Z., Kohlschmidt, J., et al. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2012.43.4738 · Cited by 415
Prediction of molecular subtypes in acute myeloid leukemia based on gene expression profiling
Verhaak, R. G. W., Wouters, B. J., Erpelinck-Verschueren, C. A. J., Abbas, S., Beverloo, H. B., Lugthart, S., Löwenberg, B., Delwel, R., & Valk, P. J. M. (2008) · Haematologica · doi:10.3324/haematol.13299 · Cited by 353
Shen, Y., Zhu, Y., Fan, X., Shi, J.-Y., Wang, Q., Yan, X., Gu, Z., Wang, Y., Chen, B., Jiang, C.-L., et al. (2011) · Blood · doi:10.1182/blood-2011-03-343988 · Cited by 329
MDS and secondary AML display unique patterns and abundance of aberrant DNA methylation
Figueroa, M. E., Skrabanek, L. A., Li, Y., Jiemjit, A., Fandy, T. E., Paietta, E. M., Fernandez, H. F., Tallman, M. S., Greally, J. M., Carraway, H. E., et al. (2009) · Blood · doi:10.1182/blood-2009-01-200519 · Cited by 325
The prognostic and functional role of microRNAs in acute myeloid leukemia
Marcucci, G., Mrózek, K., Radmacher, M. D., Garzon, R., & Bloomfield, C. D. (2010) · Blood · doi:10.1182/blood-2010-09-191312 · Cited by 274
Array-based genomic resequencing of human leukemia
Yamashita, Y., Yuan, J., Suetake, I., Suzuki, H., Ishikawa, Y., Choi, Y. L., Ueno, T., Soda, M., Hamada, T., Haruta, H., et al. (2010) · Oncogene · doi:10.1038/onc.2010.117 · Cited by 259
Acquired copy number alterations in adult acute myeloid leukemia genomes
Walter, M. J., Payton, J. E., Ries, R. E., Shannon, W. D., Deshmukh, H., Zhao, Y., Baty, J., Heath, S. E., Westervelt, P., Watson, M. A., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0903091106 · Cited by 251
Hematopoietic-specific microRNA expression in human cells
Ramkissoon, S. H., Mainwaring, L. A., Ogasawara, Y., Keyvanfar, K., McCoy, J. P., Sloand, E. M., Kajigaya, S., & Young, N. S. (2005) · Leukemia Research · doi:10.1016/j.leukres.2005.09.001 · Cited by 241
Lv, M., Zhang, X., Jia, H., Li, D., Zhang, B., Zhang, H., Hong, M., Jiang, T., Jiang, Q., Lu, J., et al. (2011) · Leukemia · doi:10.1038/leu.2011.273 · Cited by 175
Wang, X., Gong, J., Yu, J., Wang, F., Zhang, X., Yin, X.-L., Tan, Z., Luo, Z.-M., Yang, G., Shen, C., et al. (2012) · Blood · doi:10.1182/blood-2011-10-385716 · Cited by 172
Bellon, M., Lepelletier, Y., Hermine, O., & Nicot, C. (2009) · Blood · doi:10.1182/blood-2008-11-189845 · Cited by 164
Cbfβ-SMMHC induces distinct abnormal myeloid progenitors able to develop acute myeloid leukemia
Kuo, Y., Landrette, S. F., Heilman, S. A., Perrat, P. N., Garrett, L. J., Liu, P. P., Beau, M. M. L., Kogan, S. C., & Castilla, L. H. (2006) · Cancer Cell · doi:10.1016/j.ccr.2005.12.014 · Cited by 152
Chromosomal translocations: revisited yet again
Rowley, J. D. (2008) · Blood · doi:10.1182/blood-2008-04-097931 · Cited by 148
Bullinger, L., Krönke, J., Schön, C., Radtke, I., Urlbauer, K., Botzenhardt, U., Gaidzik, V., Carió, A., Senger, C., Schlenk, R. F., et al. (2009) · Leukemia · doi:10.1038/leu.2009.263 · Cited by 141
Westervelt, P., Lane, A. A., Pollock, J. L., et al. (2003) · Blood · doi:10.1182/blood-2002-12-3779 · Cited by 138
Specific small nucleolar RNA expression profiles in acute leukemia
Valleron, W., Laprévotte, E., Gautier, E., Quelen, C., Demur, C., Delabesse, É., Agirre, X., Prósper, F., Kiss, T., & Brousset, P. (2012) · Leukemia · doi:10.1038/leu.2012.111 · Cited by 137
Payton, J. E., Grieselhuber, N. R., Chang, L., Murakami, M. A., Geiss, G. K., Link, D. C., Nagarajan, R., Watson, M. A., & Ley, T. J. (2009) · Journal of Clinical Investigation · doi:10.1172/jci38248 · Cited by 137
Molecular genetics in acute myeloid leukemia
Bacher, U., Schnittger, S., & Haferlach, T. (2010) · Current Opinion in Oncology · doi:10.1097/cco.0b013e32833ed806 · Cited by 80
DIFFERENTIAL microRNA EXPRESSION IN CHILDHOOD B-CELL PRECURSOR ACUTE LYMPHOBLASTIC LEUKEMIA
Ju, X., Li, D., Shi, Q., Hou, H., Sun, N., & Shen, B.-J. (2009) · Pediatric Hematology and Oncology · doi:10.1080/08880010802378338 · Cited by 78
Bryant, A. J., Palma, C. A., Jayaswal, V., Yang, Y. W., Lutherborrow, M. A., & David, D. F. (2012) · Molecular Cancer · doi:10.1186/1476-4598-11-8 · Cited by 73
Faraoni, I., Laterza, S., Ardiri, D., Ciardi, C., Fazi, F., & Lo‐Coco, F. (2012) · Journal of Hematology & Oncology · doi:10.1186/1756-8722-5-26 · Cited by 71
Ovcharenko, D., Stölzel, F., Poitz, D. M., Fierro, F. A., Schaich, M. A., Neubauer, A., Kelnar, K., Davison, T. S., Müller‐Tidow, C., Thiede, C., et al. (2011) · Experimental Hematology · doi:10.1016/j.exphem.2011.07.008 · Cited by 47
DNA profiling by arrayCGH in acute myeloid leukemia and myelodysplastic syndromes
Suela, J., Álvarez, S., & Cigudosa, J. C. (2007) · Cytogenetic and Genome Research · doi:10.1159/000108314 · Cited by 46
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Metadata
- Authors
- The Cancer Genome Atlas Research Network
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- The Cancer Genome Atlas Research Network
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2013-05-30
- Volume
- 368
- Issue
- 22
- Pages
- 2059-2074
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC3767041
- OpenAlex
- W1255676896
- Cited by
- 5,078
- References
- 49
- Citations by year
- 2026: 195 · 2025: 277 · 2024: 335 · 2023: 415 · 2022: 465 · 2021: 509 · 2020: 485 · 2019: 466 · 2018: 361 · 2017: 424 · 2016: 382 · 2015: 343 · 2014: 304 · 2013: 108
- FWCI
- 271.87
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- eSpace (Curtin University) (submittedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- Funders
- National Institutes of Health
- National Human Genome Research Institute (U54HG003067, U54HG003079, U54HG003273, R01HG005690)
- National Cancer Institute (R01CA083962, U24CA143882, U24CA143843, U24CA143840, U24CA143858, U24CA144025, U24CA143866, U24CA143883, U24CA143845, R01CA162086, U24CA143867, U24CA143848, U24CA143799, U24CA143835, P01CA101937, P30CA016672, P30CA091842)
- Topics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- acute myeloid leukemia, de novo AML, adult AML, somatic mutations, epigenetics, DNA methylation, transcription factor fusion, NPM1, tumor suppressor, chromatin modifiers, driver mutations, risk stratification
- MeSH terms
- Nucleophosmin, Adult, Female, Humans, Male, Middle Aged, Mutation, Leukemia, Myeloid, Acute, Gene Expression, Genome, Human, Sequence Analysis, DNA, CpG Islands, DNA Methylation, MicroRNAs, Gene Fusion, Epigenomics
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