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Circulating Tumour DNA Analysis for Tumour Genome Characterisation and Monitoring Disease Burden in Extramedullary Multiple Myeloma

Mutational characterisation in extramedullary multiple myeloma (EM-MM) patients is challenging due to inaccessible EM plasmacytomas, unsafe nature of multiple biopsies and the spatial and temporal genomic heterogeneity apparent in MM (Graphical abstract). Conventional monitoring of disease burden is...

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Autores principales: Mithraprabhu, Sridurga, Sirdesai, Shreerang, Chen, Maoshan, Khong, Tiffany, Spencer, Andrew
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6073672/
https://www.ncbi.nlm.nih.gov/pubmed/29937522
http://dx.doi.org/10.3390/ijms19071858
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author Mithraprabhu, Sridurga
Sirdesai, Shreerang
Chen, Maoshan
Khong, Tiffany
Spencer, Andrew
author_facet Mithraprabhu, Sridurga
Sirdesai, Shreerang
Chen, Maoshan
Khong, Tiffany
Spencer, Andrew
author_sort Mithraprabhu, Sridurga
collection PubMed
description Mutational characterisation in extramedullary multiple myeloma (EM-MM) patients is challenging due to inaccessible EM plasmacytomas, unsafe nature of multiple biopsies and the spatial and temporal genomic heterogeneity apparent in MM (Graphical abstract). Conventional monitoring of disease burden is through serum markers and PET-CT, however these modalities are sometimes inadequate (serum markers), not performed in a timely manner (PET-CT) and uninformative for identifying mutations driving disease progression. DNA released into the blood by tumour cells (ctDNA) contains the predominant clones derived from the multiple disease foci. Blood-derived ctDNA can, therefore, provide a holistic illustration of the major drivers of disease progression. In this report, the utility of ctDNA, as an adjunct to currently available modalities in EM-MM, is presented for a patient with EM and oligosecretory (OS) disease. Whole exome sequencing of contemporaneously acquired tumour tissue and matched ctDNA samples revealed the presence of spatial and temporal genetic heterogeneity and the identification of pathways associated with drug resistance. Longitudinal monitoring of plasma samples revealed that ctDNA can be utilised to define the dynamic clonal evolution co-existent with disease progression and as an adjunct non-invasive marker of tumour burden.
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spelling pubmed-60736722018-08-13 Circulating Tumour DNA Analysis for Tumour Genome Characterisation and Monitoring Disease Burden in Extramedullary Multiple Myeloma Mithraprabhu, Sridurga Sirdesai, Shreerang Chen, Maoshan Khong, Tiffany Spencer, Andrew Int J Mol Sci Case Report Mutational characterisation in extramedullary multiple myeloma (EM-MM) patients is challenging due to inaccessible EM plasmacytomas, unsafe nature of multiple biopsies and the spatial and temporal genomic heterogeneity apparent in MM (Graphical abstract). Conventional monitoring of disease burden is through serum markers and PET-CT, however these modalities are sometimes inadequate (serum markers), not performed in a timely manner (PET-CT) and uninformative for identifying mutations driving disease progression. DNA released into the blood by tumour cells (ctDNA) contains the predominant clones derived from the multiple disease foci. Blood-derived ctDNA can, therefore, provide a holistic illustration of the major drivers of disease progression. In this report, the utility of ctDNA, as an adjunct to currently available modalities in EM-MM, is presented for a patient with EM and oligosecretory (OS) disease. Whole exome sequencing of contemporaneously acquired tumour tissue and matched ctDNA samples revealed the presence of spatial and temporal genetic heterogeneity and the identification of pathways associated with drug resistance. Longitudinal monitoring of plasma samples revealed that ctDNA can be utilised to define the dynamic clonal evolution co-existent with disease progression and as an adjunct non-invasive marker of tumour burden. MDPI 2018-06-24 /pmc/articles/PMC6073672/ /pubmed/29937522 http://dx.doi.org/10.3390/ijms19071858 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Case Report
Mithraprabhu, Sridurga
Sirdesai, Shreerang
Chen, Maoshan
Khong, Tiffany
Spencer, Andrew
Circulating Tumour DNA Analysis for Tumour Genome Characterisation and Monitoring Disease Burden in Extramedullary Multiple Myeloma
title Circulating Tumour DNA Analysis for Tumour Genome Characterisation and Monitoring Disease Burden in Extramedullary Multiple Myeloma
title_full Circulating Tumour DNA Analysis for Tumour Genome Characterisation and Monitoring Disease Burden in Extramedullary Multiple Myeloma
title_fullStr Circulating Tumour DNA Analysis for Tumour Genome Characterisation and Monitoring Disease Burden in Extramedullary Multiple Myeloma
title_full_unstemmed Circulating Tumour DNA Analysis for Tumour Genome Characterisation and Monitoring Disease Burden in Extramedullary Multiple Myeloma
title_short Circulating Tumour DNA Analysis for Tumour Genome Characterisation and Monitoring Disease Burden in Extramedullary Multiple Myeloma
title_sort circulating tumour dna analysis for tumour genome characterisation and monitoring disease burden in extramedullary multiple myeloma
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6073672/
https://www.ncbi.nlm.nih.gov/pubmed/29937522
http://dx.doi.org/10.3390/ijms19071858
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