Longitudinal analysis of 25 sequential sample-pairs using a custom multiple myeloma mutation sequencing panel (M(3)P).
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.
Division of Hematology - Oncology, Mayo Clinic, Scottsdale, AZ, USA.
K M
KM
Kortüm
C
C
Langer
J
J
Monge
L
L
Bruins
Y X
YX
Zhu
C X
CX
Shi
P
P
Jedlowski
J B
JB
Egan
J
J
Ojha
L
L
Bullinger
M
M
Kull
G
G
Ahmann
L
L
Rasche
S
S
Knop
R
R
Fonseca
H
H
Einsele
A K
AK
Stewart
Esteban
E
Braggio
D006801:Humans; D008137:Longitudinal Studies; D009101:Multiple Myeloma / Q000175:diagnosis* / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods / Q000639:trends*