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Identification of novel fusion transcripts in multiple myeloma
  1. Mingxuan Lin1,
  2. Peak Ling Lee2,
  3. Lily Chiu1,
  4. Constance Chua2,
  5. Kenneth H K Ban3,
  6. Adeline H F Lin4,
  7. Zit Liang Chan5,
  8. Tae-Hoon Chung5,
  9. Benedict Yan1,6,
  10. Wee-Joo Chng4,5,7
  1. 1Department of Laboratory Medicine, Molecular Diagnosis Centre, National University Health System, Singapore, Singapore
  2. 2Department of Laboratory Medicine, Cytogenetics Laboratory, National University Health System, Singapore, Singapore
  3. 3Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
  4. 4Department of Haematology-Oncology, National University Cancer Institute, National University Health System, Singapore, Singapore
  5. 5Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore
  6. 6Translational Centre for Development and Research, National University Health System, Singapore, Singapore
  7. 7Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
  1. Correspondence to Dr Benedict Yan, Department of Laboratory Medicine, Molecular Diagnosis Centre, National University Health System, 119074 Singapore; benedict_yan{at}nuhs.edu.sg and Dr Wee-Joo Chng, Department of Haematology-Oncology, National University Cancer Institute, National University Health System, 119074 Singapore; mdccwj{at}nus.edu.sg

Abstract

Aims Multiple myeloma (MM) is a heterogeneous disease characterised by genetically complex abnormalities. The classical mutational spectrum includes recurrent chromosomal aberrations and gene-level mutations. Recurrent translocations involving the IGH gene such as t(11;14), t(4;14) and t(14;16) are well known. However, the presence of complex genetic abnormalities raises the possibility that fusions other than the recurrent IGH translocations exist. We therefore employed a targeted RNA-sequencing panel to identify novel putative fusions in a local cohort of MM.

Methods Targeted RNA-sequencing was performed on 21 patient samples using the Illumina TruSight RNA Pan-Cancer Panel (comprising 1385 genes). Fusion calls were generated from the Illumina RNA-Sequencing Alignment software (V.1.0.0). These samples had conventional cytogenetic and fluorescence in situ hybridisation data for the common recurrent chromosomal abnormalities (t(11;14), t(4;14), t(14;16) and 17p13 deletion). The MMRF CoMMpass dataset was analysed using the TopHat-fusion pipeline.

Results A total of 10 novel fusions were identified by the TruSight RNA Pan-Cancer Panel. Two of these fusions, HGF/CACNA2D1 and SMC3/MXI1, were validated by reverse transcription PCR and Sanger sequencing as they involve genes that may have biological relevance in MM genesis. Four of these (MAP2K4/MAP2K4P1) are likely to be spurious secondary to misalignment of reads to a pseudogene. One record of the HGF/CACNA2D1 fusion was identified from the MMRF CoMMpass dataset.

Conclusions The identification of novel fusions offers insights into the biology of MM and might have clinical relevance. Further functional studies are required to determine the biological and clinical relevance of these novel fusions.

  • myeloma
  • haem-oncology
  • cytogenetics

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Footnotes

  • Handling editor Mary Frances McMullin.

  • Contributor ML, BY and W-JC conceptualized the study. ML, PLL, LC, CC, KHKB, T-HC performed the analysis and interpretation. AHFL and ZLC organised the clinical samples. ML and BY wrote the manuscript.

  • Funding This study was partially supported by the NUHS Clinician Research Grant (grant number NUHSRO/2016/026/CRG/05) from the NUHS Research Office awarded to Benedict Yan.

  • Competing interests None declared.

  • Ethics approval Domain Specific Review Board (DSRB reference number 2012/00058).

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

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