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Novel genomic findings in multiple myeloma identified through routine diagnostic sequencing
  1. Georgina L Ryland1,
  2. Kate Jones1,
  3. Melody Chin2,
  4. John Markham3,
  5. Elle Aydogan1,
  6. Yamuna Kankanige1,
  7. Marisa Caruso4,
  8. Jerick Guinto1,
  9. Michael Dickinson4,5,
  10. H Miles Prince4,5,
  11. Kwee Yong2,
  12. Piers Blombery1,5
  1. 1 Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
  2. 2 Department of Haematology, University College London Cancer Institute, London, UK
  3. 3 Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
  4. 4 Department of Haematology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
  5. 5 Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia
  1. Correspondence to Dr Piers Blombery, Department of Pathology, Peter MacCallum Cancer Centre, 305 Grattan St, Melbourne, Victoria, 3000, Australia; piers.blombery{at}


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.

  • myeloma
  • cancer genetics
  • haemato-oncology
  • molecular pathology
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  • Handling editor Runjan Chetty.

  • Contributors GLR, KJ, MD, HMP and PB contributed to study concept. GLR, KJ and JG performed the experiments. GLR, KJ, JM, YK and PB analysed the data. MeC, MaC and KY contributed clinical samples and collected clinical data. GLR and PB drafted the manuscript. All authors approved the final version of the manuscript.

  • Funding We gratefully acknowledge funding support from The Snowdome Foundation ( and Vision Super (

  • Competing interests None declared.

  • Patient consent Not required.

  • Ethics approval This study was performed with approval from the ethics committee of the Peter MacCallum Cancer Centre and the National Research Ethics Service Committee London.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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