Haematologica (Sep 2017)

The spectrum of somatic mutations in monoclonal gammopathy of undetermined significance indicates a less complex genomic landscape than that in multiple myeloma

  • Aneta Mikulasova,
  • Christopher P. Wardell,
  • Alexander Murison,
  • Eileen M. Boyle,
  • Graham H. Jackson,
  • Jan Smetana,
  • Zuzana Kufova,
  • Ludek Pour,
  • Viera Sandecka,
  • Martina Almasi,
  • Pavla Vsianska,
  • Evzen Gregora,
  • Petr Kuglik,
  • Roman Hajek,
  • Faith E. Davies,
  • Gareth J. Morgan,
  • Brian A. Walker

DOI
https://doi.org/10.3324/haematol.2017.163766
Journal volume & issue
Vol. 102, no. 9

Abstract

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Monoclonal gammopathy of undetermined significance is a pre-malignant precursor of multiple myeloma with a 1% risk of progression per year. Although targeted analyses have shown the presence of specific genetic abnormalities such as IGH translocations, RB1 deletion, 1q gain, hyperdiploidy or RAS gene mutations, little is known about the molecular mechanism of malignant transformation. We performed whole exome sequencing together with comparative genomic hybridization plus single nucleotide polymorphism array analysis in 33 flow-cytometry-separated abnormal plasma cell samples from patients with monoclonal gammopathy of undetermined significance to describe somatic gene mutations and chromosome changes at the genome-wide level. Non-synonymous mutations and copy-number alterations were present in 97.0% and in 60.6% of cases, respectively. Importantly, the number of somatic mutations was significantly lower in monoclonal gammopathy of undetermined significance than in myeloma (P