Exosomes from Plasma of Neuroblastoma Patients Contain Doublestranded DNA Reflecting the Mutational Status of Parental Tumor Cells
Neuroblastoma (NB) is an aggressive infancy tumor, leading cause of death among preschool age diseases. Here we focused on characterization of exosomal DNA (exo-DNA) isolated from plasma cell-derived exosomes of neuroblastoma patients, and its potential use for detection of somatic mutations present...
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| Format: | Article |
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MDPI AG
2021-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/7/3667 |
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| author | Chiara Degli Esposti Barbara Iadarola Simone Maestri Cristina Beltrami Denise Lavezzari Martina Morini Patrizia De Marco Giovanni Erminio Alberto Garaventa Federico Zara Massimo Delledonne Marzia Ognibene Annalisa Pezzolo |
| author_facet | Chiara Degli Esposti Barbara Iadarola Simone Maestri Cristina Beltrami Denise Lavezzari Martina Morini Patrizia De Marco Giovanni Erminio Alberto Garaventa Federico Zara Massimo Delledonne Marzia Ognibene Annalisa Pezzolo |
| author_sort | Chiara Degli Esposti |
| collection | DOAJ |
| description | Neuroblastoma (NB) is an aggressive infancy tumor, leading cause of death among preschool age diseases. Here we focused on characterization of exosomal DNA (exo-DNA) isolated from plasma cell-derived exosomes of neuroblastoma patients, and its potential use for detection of somatic mutations present in the parental tumor cells. Exosomes are small extracellular membrane vesicles secreted by most cells, playing an important role in intercellular communications. Using an enzymatic method, we provided evidence for the presence of double-stranded DNA in the NB exosomes. Moreover, by whole exome sequencing, we demonstrated that NB exo-DNA represents the entire exome and that it carries tumor-specific genetic mutations, including those occurring on known oncogenes and tumor suppressor genes in neuroblastoma (<i>ALK</i>, <i>CHD5</i>, <i>SHANK2</i>, <i>PHOX2B</i>, <i>TERT</i>, <i>FGFR1</i>, and <i>BRAF</i>). NB exo-DNA can be useful to identify variants responsible for acquired resistance, such as mutations of <i>ALK</i>, <i>TP53</i>, and <i>RAS</i>/<i>MAPK</i> genes that appear in relapsed patients. The possibility to isolate and to enrich NB derived exosomes from plasma using surface markers, and the quick and easy extraction of exo-DNA, gives this methodology a translational potential in the clinic. Exo-DNA can be an attractive non-invasive biomarker for NB molecular diagnostic, especially when tissue biopsy cannot be easily available. |
| first_indexed | 2024-03-10T12:42:46Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T12:42:46Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a3c9487e4e0e4fe99ec9483e1b47f72f2023-11-21T13:46:44ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-04-01227366710.3390/ijms22073667Exosomes from Plasma of Neuroblastoma Patients Contain Doublestranded DNA Reflecting the Mutational Status of Parental Tumor CellsChiara Degli Esposti0Barbara Iadarola1Simone Maestri2Cristina Beltrami3Denise Lavezzari4Martina Morini5Patrizia De Marco6Giovanni Erminio7Alberto Garaventa8Federico Zara9Massimo Delledonne10Marzia Ognibene11Annalisa Pezzolo12Dipartimento di Biotecnologie, Università degli Studi di Verona, 37134 Verona, ItalyDipartimento di Biotecnologie, Università degli Studi di Verona, 37134 Verona, ItalyDipartimento di Biotecnologie, Università degli Studi di Verona, 37134 Verona, ItalyDipartimento di Biotecnologie, Università degli Studi di Verona, 37134 Verona, ItalyDipartimento di Biotecnologie, Università degli Studi di Verona, 37134 Verona, ItalyLaboratorio di Biologia Molecolare, IRCCS Giannina Gaslini, 16147 Genova, ItalyU.O.C. Genetica Medica, IRCCS Giannina Gaslini, 16147 Genova, ItalyEpidemiologia e Biostatistica, IRCCS Giannina Gaslini, 16147 Genova, ItalyDivisione di Oncologia, IRCCS Giannina Gaslini, 16147 Genova, ItalyU.O.C. Genetica Medica, IRCCS Giannina Gaslini, 16147 Genova, ItalyDipartimento di Biotecnologie, Università degli Studi di Verona, 37134 Verona, ItalyU.O.C. Genetica Medica, IRCCS Giannina Gaslini, 16147 Genova, ItalyIRCCS Giannina Gaslini, 16147 Genova, ItalyNeuroblastoma (NB) is an aggressive infancy tumor, leading cause of death among preschool age diseases. Here we focused on characterization of exosomal DNA (exo-DNA) isolated from plasma cell-derived exosomes of neuroblastoma patients, and its potential use for detection of somatic mutations present in the parental tumor cells. Exosomes are small extracellular membrane vesicles secreted by most cells, playing an important role in intercellular communications. Using an enzymatic method, we provided evidence for the presence of double-stranded DNA in the NB exosomes. Moreover, by whole exome sequencing, we demonstrated that NB exo-DNA represents the entire exome and that it carries tumor-specific genetic mutations, including those occurring on known oncogenes and tumor suppressor genes in neuroblastoma (<i>ALK</i>, <i>CHD5</i>, <i>SHANK2</i>, <i>PHOX2B</i>, <i>TERT</i>, <i>FGFR1</i>, and <i>BRAF</i>). NB exo-DNA can be useful to identify variants responsible for acquired resistance, such as mutations of <i>ALK</i>, <i>TP53</i>, and <i>RAS</i>/<i>MAPK</i> genes that appear in relapsed patients. The possibility to isolate and to enrich NB derived exosomes from plasma using surface markers, and the quick and easy extraction of exo-DNA, gives this methodology a translational potential in the clinic. Exo-DNA can be an attractive non-invasive biomarker for NB molecular diagnostic, especially when tissue biopsy cannot be easily available.https://www.mdpi.com/1422-0067/22/7/3667neuroblastomaexosomesexo-DNA<i>ALK</i>genotypabilitytumor mutation load |
| spellingShingle | Chiara Degli Esposti Barbara Iadarola Simone Maestri Cristina Beltrami Denise Lavezzari Martina Morini Patrizia De Marco Giovanni Erminio Alberto Garaventa Federico Zara Massimo Delledonne Marzia Ognibene Annalisa Pezzolo Exosomes from Plasma of Neuroblastoma Patients Contain Doublestranded DNA Reflecting the Mutational Status of Parental Tumor Cells International Journal of Molecular Sciences neuroblastoma exosomes exo-DNA <i>ALK</i> genotypability tumor mutation load |
| title | Exosomes from Plasma of Neuroblastoma Patients Contain Doublestranded DNA Reflecting the Mutational Status of Parental Tumor Cells |
| title_full | Exosomes from Plasma of Neuroblastoma Patients Contain Doublestranded DNA Reflecting the Mutational Status of Parental Tumor Cells |
| title_fullStr | Exosomes from Plasma of Neuroblastoma Patients Contain Doublestranded DNA Reflecting the Mutational Status of Parental Tumor Cells |
| title_full_unstemmed | Exosomes from Plasma of Neuroblastoma Patients Contain Doublestranded DNA Reflecting the Mutational Status of Parental Tumor Cells |
| title_short | Exosomes from Plasma of Neuroblastoma Patients Contain Doublestranded DNA Reflecting the Mutational Status of Parental Tumor Cells |
| title_sort | exosomes from plasma of neuroblastoma patients contain doublestranded dna reflecting the mutational status of parental tumor cells |
| topic | neuroblastoma exosomes exo-DNA <i>ALK</i> genotypability tumor mutation load |
| url | https://www.mdpi.com/1422-0067/22/7/3667 |
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