Ryland, GL;
Jones, K;
Chin, M;
Markham, J;
Aydogan, E;
Kankanige, Y;
Caruso, M;
... Blombery, P; + view all
(2018)
Novel genomic findings in multiple myeloma identified through routine diagnostic sequencing.
Journal of Clinical Pathology
, 71
(10)
pp. 895-899.
10.1136/jclinpath-2018-205195.
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Abstract
Aims: Multiple myeloma is a genomically complex haematological malignancy with many genomic alterations recognised as important in diagnosis, prognosis and therapeutic decision making. Here, we provide a summary of genomic findings identified through routine diagnostic next-generation sequencing at our centre. // Methods: A cohort of 86 patients with multiple myeloma underwent diagnostic sequencing using a custom hybridisation-based panel targeting 104 genes. Sequence variants, genome-wide copy number changes and structural rearrangements were detected using an inhouse-developed bioinformatics pipeline. // Results: At least one mutation was found in 69 (80%) patients. Frequently mutated genes included TP53 (36%), KRAS (22.1%), NRAS (15.1%), FAM46C/DIS3 (8.1%) and TET2/FGFR3 (5.8%), including multiple mutations not previously described in myeloma. Importantly we observed TP53 mutations in the absence of a 17 p deletion in 8% of the cohort, highlighting the need for sequencing-based assessment in addition to cytogenetics to identify these high-risk patients. Multiple novel copy number changes and immunoglobulin heavy chain translocations are also discussed. // Conclusions: Our results demonstrate that many clinically relevant genomic findings remain in multiple myeloma which have not yet been identified through large-scale sequencing efforts, and provide important mechanistic insights into plasma cell pathobiology.
| Type: | Article |
|---|---|
| Title: | Novel genomic findings in multiple myeloma identified through routine diagnostic sequencing |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1136/jclinpath-2018-205195 |
| Publisher version: | http://dx.doi.org/10.1136/jclinpath-2018-205195 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | multiple myeloma; genomics; mutation; high throughput sequencing; copy number; immunoglobulin heavy chain; translocation |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10081284 |
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