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Detection of MDM2 amplification by shallow whole genome sequencing of cell-free DNA of patients with dedifferentiated liposarcoma

High-level amplification of MDM2 and other genes in the 12q13–15 locus is a hallmark genetic feature of well-differentiated and dedifferentiated liposarcomas (WDLPS and DDLPS, respectively). Detection of this genomic aberration in plasma cell-free DNA may be a clinically useful assay for non-invasiv...

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Autores principales: Przybyl, Joanna, Spans, Lien, Ganjoo, Kristen, Bui, Nam, Mohler, David, Norton, Jeffrey, Poultsides, George, Debiec-Rychter, Maria, van de Rijn, Matt
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8730389/
https://www.ncbi.nlm.nih.gov/pubmed/34986184
http://dx.doi.org/10.1371/journal.pone.0262272
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author Przybyl, Joanna
Spans, Lien
Ganjoo, Kristen
Bui, Nam
Mohler, David
Norton, Jeffrey
Poultsides, George
Debiec-Rychter, Maria
van de Rijn, Matt
author_facet Przybyl, Joanna
Spans, Lien
Ganjoo, Kristen
Bui, Nam
Mohler, David
Norton, Jeffrey
Poultsides, George
Debiec-Rychter, Maria
van de Rijn, Matt
author_sort Przybyl, Joanna
collection PubMed
description High-level amplification of MDM2 and other genes in the 12q13–15 locus is a hallmark genetic feature of well-differentiated and dedifferentiated liposarcomas (WDLPS and DDLPS, respectively). Detection of this genomic aberration in plasma cell-free DNA may be a clinically useful assay for non-invasive distinction between these liposarcomas and other retroperitoneal tumors in differential diagnosis, and might be useful for the early detection of disease recurrence. In this study, we performed shallow whole genome sequencing of cell-free DNA extracted from 10 plasma samples from 3 patients with DDLPS and 1 patient with WDLPS. In addition, we studied 31 plasma samples from 11 patients with other types of soft tissue tumors. We detected MDM2 amplification in cell-free DNA of 2 of 3 patients with DDLPS. By applying a genome-wide approach to the analysis of cell-free DNA, we also detected amplification of other genes that are known to be recurrently affected in DDLPS. Based on the analysis of one patient with DDLPS with longitudinal plasma samples available, we show that tracking MDM2 amplification in cell-free DNA may be potentially useful for evaluation of response to treatment. The patient with WDLPS and patients with other soft tissue tumors in differential diagnosis were negative for the MDM2 amplification in cell-free DNA. In summary, we demonstrate the feasibility of detecting amplification of MDM2 and other DDLPS-associated genes in plasma cell-free DNA using technology that is already routinely applied for other clinical indications. Our results may have clinical implications for improved diagnosis and surveillance of patients with retroperitoneal tumors.
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spelling pubmed-87303892022-01-06 Detection of MDM2 amplification by shallow whole genome sequencing of cell-free DNA of patients with dedifferentiated liposarcoma Przybyl, Joanna Spans, Lien Ganjoo, Kristen Bui, Nam Mohler, David Norton, Jeffrey Poultsides, George Debiec-Rychter, Maria van de Rijn, Matt PLoS One Research Article High-level amplification of MDM2 and other genes in the 12q13–15 locus is a hallmark genetic feature of well-differentiated and dedifferentiated liposarcomas (WDLPS and DDLPS, respectively). Detection of this genomic aberration in plasma cell-free DNA may be a clinically useful assay for non-invasive distinction between these liposarcomas and other retroperitoneal tumors in differential diagnosis, and might be useful for the early detection of disease recurrence. In this study, we performed shallow whole genome sequencing of cell-free DNA extracted from 10 plasma samples from 3 patients with DDLPS and 1 patient with WDLPS. In addition, we studied 31 plasma samples from 11 patients with other types of soft tissue tumors. We detected MDM2 amplification in cell-free DNA of 2 of 3 patients with DDLPS. By applying a genome-wide approach to the analysis of cell-free DNA, we also detected amplification of other genes that are known to be recurrently affected in DDLPS. Based on the analysis of one patient with DDLPS with longitudinal plasma samples available, we show that tracking MDM2 amplification in cell-free DNA may be potentially useful for evaluation of response to treatment. The patient with WDLPS and patients with other soft tissue tumors in differential diagnosis were negative for the MDM2 amplification in cell-free DNA. In summary, we demonstrate the feasibility of detecting amplification of MDM2 and other DDLPS-associated genes in plasma cell-free DNA using technology that is already routinely applied for other clinical indications. Our results may have clinical implications for improved diagnosis and surveillance of patients with retroperitoneal tumors. Public Library of Science 2022-01-05 /pmc/articles/PMC8730389/ /pubmed/34986184 http://dx.doi.org/10.1371/journal.pone.0262272 Text en © 2022 Przybyl et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Przybyl, Joanna
Spans, Lien
Ganjoo, Kristen
Bui, Nam
Mohler, David
Norton, Jeffrey
Poultsides, George
Debiec-Rychter, Maria
van de Rijn, Matt
Detection of MDM2 amplification by shallow whole genome sequencing of cell-free DNA of patients with dedifferentiated liposarcoma
title Detection of MDM2 amplification by shallow whole genome sequencing of cell-free DNA of patients with dedifferentiated liposarcoma
title_full Detection of MDM2 amplification by shallow whole genome sequencing of cell-free DNA of patients with dedifferentiated liposarcoma
title_fullStr Detection of MDM2 amplification by shallow whole genome sequencing of cell-free DNA of patients with dedifferentiated liposarcoma
title_full_unstemmed Detection of MDM2 amplification by shallow whole genome sequencing of cell-free DNA of patients with dedifferentiated liposarcoma
title_short Detection of MDM2 amplification by shallow whole genome sequencing of cell-free DNA of patients with dedifferentiated liposarcoma
title_sort detection of mdm2 amplification by shallow whole genome sequencing of cell-free dna of patients with dedifferentiated liposarcoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8730389/
https://www.ncbi.nlm.nih.gov/pubmed/34986184
http://dx.doi.org/10.1371/journal.pone.0262272
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