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ERG amplification is a secondary recurrent driver event in myeloid malignancy with complex karyotype and TP53 mutations
dc.contributor.authorLee, Winston Y.
dc.contributor.authorGutierrez-Lanz, Efrain A.
dc.contributor.authorXiao, Hong
dc.contributor.authorMcClintock, David
dc.contributor.authorChan, May P.
dc.contributor.authorBixby, Dale L.
dc.contributor.authorShao, Lina
dc.date.accessioned2022-06-01T20:29:39Z
dc.date.available2023-08-01 16:29:33en
dc.date.available2022-06-01T20:29:39Z
dc.date.issued2022-07
dc.identifier.citationLee, Winston Y.; Gutierrez-Lanz, Efrain A. ; Xiao, Hong; McClintock, David; Chan, May P.; Bixby, Dale L.; Shao, Lina (2022). "ERG amplification is a secondary recurrent driver event in myeloid malignancy with complex karyotype and TP53 mutations." Genes, Chromosomes and Cancer 61(7): 399-411.
dc.identifier.issn1045-2257
dc.identifier.issn1098-2264
dc.identifier.urihttps://hdl.handle.net/2027.42/172824
dc.description.abstractERG is a transcription factor encoded on chromosome 21q22.2 with important roles in hematopoiesis and oncogenesis of prostate cancer. ERG amplification has been identified as one of the most common recurrent events in acute myeloid leukemia with complex karyotype (AML-CK). In this study, we uncover three different modes of ERG amplification in AML-CK. Importantly, we present evidence to show that ERG amplification is distinct from intrachromosomal amplification of chromosome 21 (iAMP21), a hallmark segmental amplification frequently encompassing RUNX1 and ERG in a subset of high-risk B-lymphoblastic leukemia. We also characterize the association with TP53 aberrations and other chromosomal aberrations, including chromothripsis. Lastly, we show that ERG amplification can initially emerge as subclonal events in low-grade myeloid neoplasms. These findings demonstrate that ERG amplification is a recurrent secondary driver event in AML and raise the tantalizing possibility of ERG as a therapeutic target.
dc.publisherJohn Wiley & Sons, Inc.
dc.subject.otheramplification
dc.subject.otherERG
dc.subject.otheriAMP21
dc.subject.otherTP53 mutation
dc.subject.othercomplex karyotype
dc.subject.otheracute myeloid leukemia
dc.titleERG amplification is a secondary recurrent driver event in myeloid malignancy with complex karyotype and TP53 mutations
dc.typeArticle
dc.rights.robotsIndexNoFollow
dc.subject.hlbsecondlevelOncology and Hematology Health Sciences
dc.subject.hlbsecondlevelGenetics
dc.subject.hlbtoplevelHealth Sciences
dc.description.peerreviewedPeer Reviewed
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/172824/1/gcc23027.pdf
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/172824/2/gcc23027_am.pdf
dc.identifier.doi10.1002/gcc.23027
dc.identifier.sourceGenes, Chromosomes and Cancer
dc.identifier.citedreferenceStephens PJ, Greenman CD, Fu B, et al. Massive genomic rearrangement acquired in a single catastrophic event during cancer development. Cell. 2011; 144 ( 1 ): 27 - 40.
dc.identifier.citedreferenceSwerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. Lyon: International Agency for Research on Cancer; 2017.
dc.identifier.citedreferencePapaemmanuil E, Gerstung M, Malcovati L, et al. Clinical and biological implications of driver mutations in myelodysplastic syndromes. Blood. 2013; 122 ( 22 ): 3616 - 3627.
dc.identifier.citedreferenceRücker FG, Schlenk RF, Bullinger L, et al. TP53 alterations in acute myeloid leukemia with complex karyotype correlate with specific copy number alterations, monosomal karyotype, and dismal outcome. Blood. 2012; 119 ( 9 ): 2114 - 2121.
dc.identifier.citedreferenceHaase D, Stevenson KE, Neuberg D, et al. TP53 mutation status divides myelodysplastic syndromes with complex karyotypes into distinct prognostic subgroups. Leukemia. 2019; 33 ( 7 ): 1747 - 1758.
dc.identifier.citedreferenceBernard E, Nannya Y, Hasserjian RP, et al. Implications of TP53 allelic state for genome stability, clinical presentation and outcomes in myelodysplastic syndromes. Nat Med. 2020; 26 ( 10 ): 1549 - 1556.
dc.identifier.citedreferenceRücker FG, Schlenk RF, Bullinger L, et al. TP53 alterations in acute myeloid leukemia with complex karyotype correlate with specific copy number alterations, monosomal karyotype, and dismal outcome. Blood. 2012; 119 ( 9 ): 2114 - 2121.
dc.identifier.citedreferenceRücker FG, Bullinger L, Schwaenen C, et al. Disclosure of candidate genes in acute myeloid leukemia with complex karyotypes using microarray-based molecular characterization. J Clin Oncol. 2006; 24 ( 24 ): 3887 - 3894.
dc.identifier.citedreferenceMrózek K, Eisfeld AK, Kohlschmidt J, et al. Complex karyotype in de novo acute myeloid leukemia: typical and atypical subtypes differ molecularly and clinically. Leukemia. 2019; 33 ( 7 ): 1620 - 1634.
dc.identifier.citedreferenceGao J, Aksoy BA, Dogrusoz U, et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal. 2013; 6 ( 269 ): pl1.
dc.identifier.citedreferenceCerami E, Gao J, Dogrusoz U, et al. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2012; 2 ( 5 ): 401 - 404.
dc.identifier.citedreferenceVan Loo P, Nordgard SH, Lingjærde OC, et al. Allele-specific copy number analysis of tumors. Proc Natl Acad Sci U S A. 2010; 107 ( 39 ): 16910 - 16915.
dc.identifier.citedreferenceGel B, Serra E. KaryoploteR: an R/Bioconductor package to plot customizable genomes displaying arbitrary data. Bioinformatics. 2017; 33 ( 19 ): 3088 - 3090.
dc.identifier.citedreferenceBankhead P, Loughrey MB, Fernández JA, et al. QuPath: open source software for digital pathology image analysis. Sci Rep. 2017; 7 ( 1 ): 16878.
dc.identifier.citedreferenceHirsch FR, Varella-Garcia M, Bunn PA, et al. Epidermal growth factor receptor in non–small-cell lung carcinomas: correlation between gene copy number and protein expression and impact on prognosis. J Clin Oncol. 2003; 21 ( 20 ): 3798 - 3807.
dc.identifier.citedreferenceJohn T, Liu G, Tsao M-S. Overview of molecular testing in non-small-cell lung cancer: mutational analysis, gene copy number, protein expression and other biomarkers of EGFR for the prediction of response to tyrosine kinase inhibitors. Oncogene. 2009; 28 ( S1 ): S14 - S23.
dc.identifier.citedreferenceGraubert TA, Shen D, Ding L, et al. Recurrent mutations in the U2AF1 splicing factor in myelodysplastic syndromes. Nat Genet. 2012; 44 ( 1 ): 53 - 57.
dc.identifier.citedreferenceFu L, Fu H, Wu Q, et al. High expression of ETS2 predicts poor prognosis in acute myeloid leukemia and may guide treatment decisions. J Transl Med. 2017; 15 ( 1 ): 1 - 9.
dc.identifier.citedreferenceAlbertson DG. Gene amplification in cancer. Trends Genet. 2006; 22 ( 8 ): 447 - 455.
dc.identifier.citedreferenceVerhaak RGW, Bafna V, Mischel PS. Extrachromosomal oncogene amplification in tumour pathogenesis and evolution. Nat Rev Cancer. 2019; 19 ( 5 ): 283 - 288.
dc.identifier.citedreferenceTanaka H, Watanabe T. Mechanisms underlying recurrent genomic amplification in human cancers. Trends in Cancer. 2020; 6 ( 6 ): 462 - 477.
dc.identifier.citedreferenceRücker FG, Dolnik A, Blätte TJ, et al. Chromothripsis is linked to TP53 alteration, cell cycle impairment, and dismal outcome in acute myeloid leukemia with complex karyotype. Haematologica. 2018; 103 ( 1 ): e17 - e20.
dc.identifier.citedreferenceBochtler T, Granzow M, Stölzel F, et al. Marker chromosomes can arise from chromothripsis and predict adverse prognosis in acute myeloid leukemia. Blood. 2017; 129 ( 10 ): 1333 - 1342.
dc.identifier.citedreferenceCortés-Ciriano I, Lee JJK, Xi R, et al. Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing. Nat Genet. 2020; 52 ( 3 ): 331 - 341.
dc.identifier.citedreferenceMoorman AV, Richards SM, Robinson HM, et al. Prognosis of children with acute lymphoblastic leukemia (ALL) and intrachromosomal amplification of chromosome 21 (iAMP21). Blood. 2007; 109 ( 6 ): 2327 - 2330.
dc.identifier.citedreferenceRand V, Parker H, Russell LJ, et al. Genomic characterization implicates iAMP21 as a likely primary genetic event in childhood B-cell precursor acute lymphoblastic leukemia. Blood. 2011; 117 ( 25 ): 6848 - 6855.
dc.identifier.citedreferenceWang X, Qiao Y, Asangani IA, et al. Development of Peptidomimetic inhibitors of the ERG gene fusion product in prostate cancer. Cancer Cell. 2017; 31 ( 4 ): 532 - 548.
dc.identifier.citedreferenceMohamed AA, Xavier CP, Sukumar G, et al. Identification of a small molecule that selectively inhibits ERG-positive cancer cell growth. Cancer Res. 2018; 78 ( 13 ): 3659 - 3671.
dc.identifier.citedreferenceWang S, Kollipara RK, Srivastava N, et al. Ablation of the oncogenic transcription factor ERG by deubiquitinase inhibition in prostate cancer. Proc Natl Acad Sci U S A. 2014; 111 ( 11 ): 4251 - 4256.
dc.identifier.citedreferenceLefebvre V, Bhattaram P. Vertebrate skeletogenesis. Curr Top Dev Biol. 2010; 90: 291 - 317.
dc.identifier.citedreferenceShah AV, Birdsey GM, Randi AM. Regulation of endothelial homeostasis, vascular development and angiogenesis by the transcription factor ERG. Vascul Pharmacol. 2016; 86: 863 - 813.
dc.identifier.citedreferenceDzierzak E, Bigas A. Blood development: hematopoietic stem cell dependence and Independence. Cell Stem Cell. 2018; 22 ( 5 ): 639 - 651.
dc.identifier.citedreferenceKnudsen KJ, Rehn M, Hasemann MS, et al. ERG promotes the maintenance of hematopoietic stem cells by restricting their differentiation. Genes Dev. 2015; 29 ( 18 ): 1915 - 1929.
dc.identifier.citedreferenceNg AP, Loughran SJ, Metcalf D, et al. Erg is required for self-renewal of hematopoietic stem cells during stress hematopoiesis in mice. Blood. 2011; 118 ( 9 ): 2454 - 2461.
dc.identifier.citedreferenceLoughran SJ, Kruse EA, Hacking DF, et al. The transcription factor erg is essential for definitive hematopoiesis and the function of adult hematopoietic stem cells. Nat Immunol. 2008; 9 ( 7 ): 810 - 819.
dc.identifier.citedreferenceTaoudi S, Bee T, Hilton A, et al. ERG dependence distinguishes developmental control of hematopoietic stem cell maintenance from hematopoietic specification. Genes Dev. 2011; 25 ( 3 ): 251 - 262.
dc.identifier.citedreferenceNg AP, Coughlan HD, Hediyeh-zadeh S, et al. An Erg-driven transcriptional program controls B cell lymphopoiesis. Nat Commun. 2020; 11 ( 1 ): 3013.
dc.identifier.citedreferenceStankiewicz MJ, Crispino JD. ETS2 and ERG promote megakaryopoiesis and synergize with alterations in GATA-1 to immortalize hematopoietic progenitor cells. Blood. 2009; 113 ( 14 ): 3337 - 3347.
dc.identifier.citedreferenceHeuston EF, Keller CA, Lichtenberg J, et al. Establishment of regulatory elements during erythro-megakaryopoiesis identifies hematopoietic lineage-commitment points. Epigenetics and Chromatin. 2018; 11 ( 1 ): 22.
dc.identifier.citedreferenceKruse EA, Loughran SJ, Baldwin TM, et al. Dual requirement for the ETS transcription factors Fli-1 and erg in hematopoietic stem cells and the megakaryocyte lineage. Proc Natl Acad Sci U S A. 2009; 106 ( 33 ): 13814 - 13819.
dc.identifier.citedreferenceTomlins SA, Laxman B, Varambally S, et al. Role of the TMPRSS2-ERG gene fusion in prostate cancer. Neoplasia. 2008; 10 ( 2 ): 177 - 188.
dc.identifier.citedreferenceMartens JHA. Acute myeloid leukemia: a central role for the ETS factor ERG. Int J Biochem Cell Biol. 2011; 43 ( 10 ): 1413 - 1416.
dc.identifier.citedreferenceMarcucci G, Baldus CD, Ruppert AS, et al. Overexpression of the ETS-related gene, ERG, predicts a worse outcome in acute myeloid leukemia with normal karyotype: a cancer and leukemia group B study. J Clin Oncol. 2005; 23 ( 36 ): 9234 - 9242.
dc.identifier.citedreferenceMetzeler KH, Dufour A, Benthaus T, et al. ERG expression is an independent prognostic factor and allows refined risk stratification in cytogenetically normal acute myeloid leukemia: a comprehensive analysis of ERG, MN1, and BAALC transcript levels using oligonucleotide microarrays. J Clin Oncol. 2009; 27 ( 30 ): 5031 - 5038.
dc.identifier.citedreferenceBaldus CD, Liyanarachchi S, Mrozek K, et al. Acute myeloid leukemia with complex karyotypes and abnormal chromosome 21: amplification discloses overexpression of APP, ETS2, and ERG genes. Proc Natl Acad Sci. 2004; 101 ( 11 ): 3915 - 3920.
dc.identifier.citedreferenceWeber S, Haferlach C, Jeromin S, et al. Gain of chromosome 21 or amplification of chromosome arm 21q is one mechanism for increased ERG expression in acute myeloid leukemia. Genes Chromosomes Cancer. 2016; 55 ( 2 ): 148 - 157.
dc.identifier.citedreferenceSotoca AM, Prange KHM, Reijnders B, et al. The oncofusion protein FUS-ERG targets key hematopoietic regulators and modulates the all-trans retinoic acid signaling pathway in t(16;21) acute myeloid leukemia. Oncogene. 2016; 35 ( 15 ): 1965 - 1976.
dc.identifier.citedreferenceHarrison CJ. Blood spotlight on iAMP21 acute lymphoblastic leukemia (ALL), a high-risk pediatric disease. Blood. 2015; 125 ( 9 ): 1383 - 1386.
dc.identifier.citedreferenceHeerema NA, Carroll AJ, Devidas M, et al. Intrachromosomal amplification of chromosome 21 is associated with inferior outcomes in children with acute lymphoblastic leukemia treated in contemporary standard-risk children’s oncology group studies: a report from the children’s oncology group. J Clin Oncol. 2013; 31 ( 27 ): 3397 - 3402.
dc.identifier.citedreferenceStrefford JC, Van Delft FW, Robinson HM, et al. Complex genomic alterations and gene expression in acute lymphoblastic leukemia with intrachromosomal amplification of chromosome 21. Proc Natl Acad Sci U S A. 2006; 103 ( 21 ): 8167 - 8172.
dc.identifier.citedreferenceLi Y, Schwab C, Ryan SL, et al. Constitutional and somatic rearrangement of chromosome 21 in acute lymphoblastic leukaemia. Nature. 2014; 508 ( 1 ): 98 - 102.
dc.identifier.citedreferenceXie W, Xu J, Hu S, et al. iAMP21 in acute myeloid leukemia is associated with complex karyotype, TP53 mutation and dismal outcome. Mod Pathol. 2020; 33: 1389 - 1397.
dc.identifier.citedreferenceMareschal S, Palau A, Lindberg J, et al. Challenging conventional karyotyping by next-generation karyotyping in 281 intensively treated patients with AML. Blood Adv. 2021; 5 ( 4 ): 1003 - 1016.
dc.working.doiNOen
dc.owningcollnameInterdisciplinary and Peer-Reviewed


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