ERG amplification is a secondary recurrent driver event in myeloid malignancy with complex karyotype and TP53 mutations

ERG amplification is a secondary recurrent driver event in myeloid malignancy with complex karyotype and TP53 mutations

ERG 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...

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Bibliographic Details
Published in:Genes chromosomes & cancer Vol. 61; no. 7; pp. 399 - 411
Main Authors: Lee, Winston Y., Gutierrez‐Lanz, Efrain A., Xiao, Hong, McClintock, David, Chan, May P., Bixby, Dale L., Shao, Lina
Format: Journal Article
Language:English
Published: Hoboken, USA John Wiley & Sons, Inc 01-07-2022
Wiley Subscription Services, Inc
Subjects:
Abnormal Karyotype
Acute myeloid leukemia
amplification
Chromosome 21
Chromosome Aberrations
complex karyotype
ERG
Humans
iAMP21
Karyotype
Karyotypes
Leukemia
Leukemia, Myeloid, Acute - pathology
Lymphatic leukemia
Male
Malignancy
Mutation
Myeloproliferative Disorders
Prostate cancer
Runx1 protein
Therapeutic targets
TP53 mutation
Transcriptional Regulator ERG - genetics
Tumor Suppressor Protein p53 - genetics
Tumorigenesis
amplification
ERG
acute myeloid leukemia
TP53 mutation
complex karyotype
iAMP21
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Summary:ERG 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.
Bibliography:Funding information
Department of Pathology, University of Michigan, Ann Arbor
ObjectType-Article-1
SourceType-Scholarly Journals-1
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content type line 23
ISSN:1045-2257
1098-2264
DOI:10.1002/gcc.23027