Longitudinal analysis of 25 sequential sample-pairs using a custom multiple myeloma mutation sequencing panel (M(3)P)

Annals of Hematology
Klaus M KortümEsteban Braggio

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 ...Continue Reading

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Citations

Oct 13, 2015·British Journal of Haematology·Marzia BarbieriMarta Lionetti
Apr 10, 2016·Nucleic Acids Research·Krzysztof KuchtaKrzysztof Ginalski
Jan 30, 2019·The Cancer Journal·Shaji K Kumar
Jun 2, 2016·American Society of Clinical Oncology Educational Book·Raphael Szalat, Nikhil C Munshi
Mar 7, 2020·Journal of Cellular and Molecular Medicine·Ana Belén HerreroNorma C Gutiérrez
Jun 16, 2016·Oncotarget·Margrethe StormFahri Saatcioglu
Mar 16, 2019·International Journal of Molecular Sciences·Leo RascheNiels Weinhold
Apr 18, 2019·Drugs in R&D·Pawel Robak, Tadeusz Robak
May 13, 2020·Blood Cancer Journal·Cecilia Bonolo de CamposA Keith Stewart
Jun 18, 2017·Cancer Research·Yuan Xiao ZhuA Keith Stewart

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