Longitudinal analysis of 25 sequential sample-pairs using a custom multiple myeloma mutation sequencing panel (M3P)

K. M. Kortüm, C. Langer, J. Monge, L. Bruins, Y. X. Zhu, C. X. Shi, P. Jedlowski, J. B. Egan, J. Ojha, L. Bullinger, M. Kull, G. Ahmann, L. Rasche, S. Knop, R. Fonseca, H. Einsele, A. K. Stewart, Esteban Braggio

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Recent advances in genomic sequencing technologies now allow results from deep next-generation sequencing to be obtained within clinically meaningful timeframes, making this an attractive approach to better guide personalized treatment strategies. No multiple myeloma-specific gene panel has been established so far; we therefore designed a 47-gene-targeting gene panel, containing 39 genes known to be mutated in ≥3 % of multiple myeloma cases and eight genes in pathways therapeutically targeted in multiple myeloma (MM). We performed targeted sequencing on tumor/germline DNA of 25 MM patients in which we also had a sequential sample post treatment. Mutation analysis revealed KRAS as the most commonly mutated gene (36 % in each time point), followed by NRAS (20 and 16 %), TP53 (16 and 16 %), DIS3 (16 and 16 %), FAM46C (12 and 16 %), and SP140 (12 and 12 %). We successfully tracked clonal evolution and identified mutation acquisition and/or loss in FAM46C, FAT1, KRAS, NRAS, SPEN, PRDM1, NEB, and TP53 as well as two mutations in XBP1, a gene associated with bortezomib resistance. Thus, we present the first longitudinal analysis of a MM-specific targeted sequencing gene panel that can be used for individual tumor characterization and for tracking clonal evolution over time.

Original languageEnglish (US)
Pages (from-to)1205-1211
Number of pages7
JournalAnnals of hematology
Volume94
Issue number7
DOIs
StatePublished - Jul 18 2015

Keywords

  • Multiple myeloma
  • Targeted sequencing

ASJC Scopus subject areas

  • Hematology

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    Kortüm, K. M., Langer, C., Monge, J., Bruins, L., Zhu, Y. X., Shi, C. X., Jedlowski, P., Egan, J. B., Ojha, J., Bullinger, L., Kull, M., Ahmann, G., Rasche, L., Knop, S., Fonseca, R., Einsele, H., Stewart, A. K., & Braggio, E. (2015). Longitudinal analysis of 25 sequential sample-pairs using a custom multiple myeloma mutation sequencing panel (M3P). Annals of hematology, 94(7), 1205-1211. https://doi.org/10.1007/s00277-015-2344-9