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Chromothripsis in acute myeloid leukemia: biological features and impact on survival
Chromothripsis is a one-step genome-shattering catastrophe resulting from disruption of one or few chromosomes in multiple fragments and consequent random rejoining and repair. This study defines incidence of chromothripsis in 395 newly diagnosed adult acute myeloid leukemia (AML) patients from thre...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6035145/ https://www.ncbi.nlm.nih.gov/pubmed/29472722 http://dx.doi.org/10.1038/s41375-018-0035-y |
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author | Fontana, Maria Chiara Marconi, Giovanni Feenstra, Jelena D. Milosevic Fonzi, Eugenio Papayannidis, Cristina Ghelli Luserna di Rorá, Andrea Padella, Antonella Solli, Vincenza Franchini, Eugenia Ottaviani, Emanuela Ferrari, Anna Baldazzi, Carmen Testoni, Nicoletta Iacobucci, Ilaria Soverini, Simona Haferlach, Torsten Guadagnuolo, Viviana Semerad, Lukas Doubek, Michael Steurer, Michael Racil, Zdenek Paolini, Stefania Manfrini, Marco Cavo, Michele Simonetti, Giorgia Kralovics, Robert Martinelli, Giovanni |
author_facet | Fontana, Maria Chiara Marconi, Giovanni Feenstra, Jelena D. Milosevic Fonzi, Eugenio Papayannidis, Cristina Ghelli Luserna di Rorá, Andrea Padella, Antonella Solli, Vincenza Franchini, Eugenia Ottaviani, Emanuela Ferrari, Anna Baldazzi, Carmen Testoni, Nicoletta Iacobucci, Ilaria Soverini, Simona Haferlach, Torsten Guadagnuolo, Viviana Semerad, Lukas Doubek, Michael Steurer, Michael Racil, Zdenek Paolini, Stefania Manfrini, Marco Cavo, Michele Simonetti, Giorgia Kralovics, Robert Martinelli, Giovanni |
author_sort | Fontana, Maria Chiara |
collection | PubMed |
description | Chromothripsis is a one-step genome-shattering catastrophe resulting from disruption of one or few chromosomes in multiple fragments and consequent random rejoining and repair. This study defines incidence of chromothripsis in 395 newly diagnosed adult acute myeloid leukemia (AML) patients from three institutions, its impact on survival and its genomic background. SNP 6.0 or CytoscanHD Array (Affymetrix(®)) were performed on all samples. We detected chromothripsis with a custom algorithm in 26/395 patients. Patients harboring chromothripsis had higher age (p = 0.002), ELN high risk (HR) (p < 0.001), lower white blood cell (WBC) count (p = 0.040), TP53 loss, and/or mutations (p < 0.001) while FLT3 (p = 0.025), and NPM1 (p = 0.032) mutations were mutually exclusive with chromothripsis. Chromothripsis-positive patients showed a worse overall survival (OS) (p < 0.001) compared with HR patients (p = 0.011) and a poor prognosis in a COX-HR optimal regression model. Chromothripsis presented the hallmarks of chromosome instability [i.e., TP53 alteration, 5q deletion, higher mean of copy number alteration (CNA), complex karyotype, alterations in DNA repair, and cell cycle] and focal deletions on chromosomes 4, 7, 12, 16, and 17. CBA. FISH showed that chromothripsis is associated with marker, derivative, and ring chromosomes. In conclusion, chromothripsis frequently occurs in AML (6.6%) and influences patient prognosis and disease biology. |
format | Online Article Text |
id | pubmed-6035145 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-60351452018-07-09 Chromothripsis in acute myeloid leukemia: biological features and impact on survival Fontana, Maria Chiara Marconi, Giovanni Feenstra, Jelena D. Milosevic Fonzi, Eugenio Papayannidis, Cristina Ghelli Luserna di Rorá, Andrea Padella, Antonella Solli, Vincenza Franchini, Eugenia Ottaviani, Emanuela Ferrari, Anna Baldazzi, Carmen Testoni, Nicoletta Iacobucci, Ilaria Soverini, Simona Haferlach, Torsten Guadagnuolo, Viviana Semerad, Lukas Doubek, Michael Steurer, Michael Racil, Zdenek Paolini, Stefania Manfrini, Marco Cavo, Michele Simonetti, Giorgia Kralovics, Robert Martinelli, Giovanni Leukemia Article Chromothripsis is a one-step genome-shattering catastrophe resulting from disruption of one or few chromosomes in multiple fragments and consequent random rejoining and repair. This study defines incidence of chromothripsis in 395 newly diagnosed adult acute myeloid leukemia (AML) patients from three institutions, its impact on survival and its genomic background. SNP 6.0 or CytoscanHD Array (Affymetrix(®)) were performed on all samples. We detected chromothripsis with a custom algorithm in 26/395 patients. Patients harboring chromothripsis had higher age (p = 0.002), ELN high risk (HR) (p < 0.001), lower white blood cell (WBC) count (p = 0.040), TP53 loss, and/or mutations (p < 0.001) while FLT3 (p = 0.025), and NPM1 (p = 0.032) mutations were mutually exclusive with chromothripsis. Chromothripsis-positive patients showed a worse overall survival (OS) (p < 0.001) compared with HR patients (p = 0.011) and a poor prognosis in a COX-HR optimal regression model. Chromothripsis presented the hallmarks of chromosome instability [i.e., TP53 alteration, 5q deletion, higher mean of copy number alteration (CNA), complex karyotype, alterations in DNA repair, and cell cycle] and focal deletions on chromosomes 4, 7, 12, 16, and 17. CBA. FISH showed that chromothripsis is associated with marker, derivative, and ring chromosomes. In conclusion, chromothripsis frequently occurs in AML (6.6%) and influences patient prognosis and disease biology. Nature Publishing Group UK 2018-02-23 2018 /pmc/articles/PMC6035145/ /pubmed/29472722 http://dx.doi.org/10.1038/s41375-018-0035-y Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, and provide a link to the Creative Commons license. You do not have permission under this license to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/. |
spellingShingle | Article Fontana, Maria Chiara Marconi, Giovanni Feenstra, Jelena D. Milosevic Fonzi, Eugenio Papayannidis, Cristina Ghelli Luserna di Rorá, Andrea Padella, Antonella Solli, Vincenza Franchini, Eugenia Ottaviani, Emanuela Ferrari, Anna Baldazzi, Carmen Testoni, Nicoletta Iacobucci, Ilaria Soverini, Simona Haferlach, Torsten Guadagnuolo, Viviana Semerad, Lukas Doubek, Michael Steurer, Michael Racil, Zdenek Paolini, Stefania Manfrini, Marco Cavo, Michele Simonetti, Giorgia Kralovics, Robert Martinelli, Giovanni Chromothripsis in acute myeloid leukemia: biological features and impact on survival |
title | Chromothripsis in acute myeloid leukemia: biological features and impact on survival |
title_full | Chromothripsis in acute myeloid leukemia: biological features and impact on survival |
title_fullStr | Chromothripsis in acute myeloid leukemia: biological features and impact on survival |
title_full_unstemmed | Chromothripsis in acute myeloid leukemia: biological features and impact on survival |
title_short | Chromothripsis in acute myeloid leukemia: biological features and impact on survival |
title_sort | chromothripsis in acute myeloid leukemia: biological features and impact on survival |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6035145/ https://www.ncbi.nlm.nih.gov/pubmed/29472722 http://dx.doi.org/10.1038/s41375-018-0035-y |
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