Highlights
- •Two concurrent chromothripsis events occurred in a patient with AML-MRC at onset.
- •We found TP53 impairment, known as promoting chromothripsis.
- •Chromothripsis and stepwise alterations concurred towards patient's poor outcome.
- •Genes involved in both aberration types showed altered expression in the patient.
Abstract
Acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) is a heterogeneous
hematological disorder defined by morphological, genetic, and clinical features. Patients
with AML-MRC often show cytogenetic changes, which are associated with poor prognosis.
Straightforward criteria for AML-MRC diagnosis and a more rigorous characterization
of the genetic abnormalities accompanying this disease are needed. Here we describe
an informative AML-MRC case, showing two separate, but concurrent, chromothripsis
events, occurred at the onset of the tumor, and originating an unbalanced t(5;7) translocation
and a derivative chromosome 12 with a highly rearranged short arm. Conversely, despite
chromothripsis has been often associated with genomic amplification in cancer, in
this case a large marker chromosome harboring amplified sequences from chromosomes
19 and 22 arose from a stepwise mechanism. Notably, the patient also showed a TP53 mutated status, known to be associated with an increased susceptibility towards chromothripsis
and a poor prognosis. Our results indicate that multiple chromothripsis events may
occur early in neoplastic transformation and act in a synergistic way with progressive
chromosomal alterations to determine a dramatic impact on disease outcome, as suggested
by the gene expression profile analysis.
Keywords
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Article Info
Publication History
Published online: June 12, 2019
Accepted:
June 11,
2019
Received in revised form:
May 30,
2019
Received:
March 30,
2019
Identification
Copyright
© 2019 Elsevier Inc. All rights reserved.
