Circulating Tumour DNA Analysis for Tumour Genome Characterisation and Monitoring Disease Burden in Extramedullary Multiple Myeloma
by
Sridurga Mithraprabhu 1,2
, Shreerang Sirdesai 2, Maoshan Chen 1,2, Tiffany Khong 1,2 and Andrew Spencer 1,2,3,*
Sridurga Mithraprabhu 1,2, Shreerang Sirdesai 2, Maoshan Chen 1,2, Tiffany Khong 1,2 and Andrew Spencer 1,2,3,*
1
Myeloma Research Group, Australian Centre for Blood Diseases, Alfred Hospital–Monash University, Melbourne 3004, Australia
2
Malignant Haematology and Stem Cell Transplantation, Alfred Hospital, Melbourne 3004, Australia
3
Department of Clinical Haematology, Monash University, Clayton 3800, Australia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(7), 1858; https://doi.org/10.3390/ijms19071858
Received: 7 June 2018 / Revised: 21 June 2018 / Accepted: 22 June 2018 / Published: 24 June 2018
(This article belongs to the Special Issue Translational Diagnostics in Lymphoproliferative and Plasma Cell Disorders)
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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Keywords:
cell-free DNA; ctDNA; extramedullary MM; whole exome sequencing; spatial heterogeneity; digital PCR
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
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MDPI and ACS Style
Mithraprabhu, S.; Sirdesai, S.; Chen, M.; Khong, T.; Spencer, A. Circulating Tumour DNA Analysis for Tumour Genome Characterisation and Monitoring Disease Burden in Extramedullary Multiple Myeloma. Int. J. Mol. Sci. 2018, 19, 1858.
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