RT Journal Article
SR Electronic
T1 Novel genomic findings in multiple myeloma identified through routine diagnostic sequencing
JF Journal of Clinical Pathology
JO J Clin Pathol
FD BMJ Publishing Group Ltd and Association of Clinical Pathologists
SP jclinpath-2018-205195
DO 10.1136/jclinpath-2018-205195
A1 Georgina L Ryland
A1 Kate Jones
A1 Melody Chin
A1 John Markham
A1 Elle Aydogan
A1 Yamuna Kankanige
A1 Marisa Caruso
A1 Jerick Guinto
A1 Michael Dickinson
A1 H Miles Prince
A1 Kwee Yong
A1 Piers Blombery
YR 2018
UL http://jcp.bmj.com/content/early/2018/05/14/jclinpath-2018-205195.abstract
AB 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.