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

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Item Type:	Article
Title:	Longitudinal analysis of 25 sequential sample-pairs using a custom multiple myeloma mutation sequencing panel (M(3)P)
Creators Name:	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. and Braggio, E.
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.
Keywords:	Multiple Myeloma, Targeted Sequencing
Source:	Annals of Hematology
ISSN:	0939-5555
Publisher:	Springer
Volume:	94
Number:	7
Page Range:	1205-1211
Date:	July 2015
Additional Information:	Copyright © Springer-Verlag Berlin Heidelberg 2015
Official Publication:	https://doi.org/10.1007/s00277-015-2344-9
External Fulltext:	View full text on PubMed Central
PubMed:	View item in PubMed

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