Figure Legends (Supplemental Tables)
S_Table 1: Clinical and cytogenetic information about the 5 primary MM cases that were
investigated in our lab by whole exome sequencing. ID: idarubicine, dexamethasone; IEV:
ifosfamide, epirubicine, etoposide; HDT Mel+autol.PBSCT: high-dose therapy with melphalan
and autologous peripheral stem cell transplantation; IFN: Gamma-interferone; VD: vincristine,
dexamethasone; BD: bortezomib, dexamethasone; RD: indicates revlimid, dexamethasone;
BCaelix: bortezomib, pegylated liposomal doxorubicin; D-BEAM carmustine, dexamethasone,
etoposide, cytarabine, melphalan, BendaD bendamustin, dexamethasone; RAD revlimid,
doxorubicine, dexamethasone; BCD bortezomib, cyclophosphamide, dexamethasone;
RituxVsEAD: rituximab, vindesine, etoposide, dexamethasone. MGUS: Monoclonal
gammopathy of undetermined significance, PC leukemia: plasma cell leukemia, BM: bone
marrow, n.a.: not available
S_Table 2: Sequencing output and quality assessment for each sample.
S_Table 3: All primers were designed using the primer design tool from Integrated DNA
Technologies (IDT) and purchased from IDT.
S_Table 4: 913 SNVs affecting genes, mutated in at least one primary MM sample (including
[5]. N: not detected; W, K, S, M, Y, R: heterozygous mutations. Numbers of normal and mutant
reads are shown in columns AE-AH. If the same mutation was found in 2, 3 or 4 cases, 2, 3 or
4 values are provided.
S_Table 5: 330 SNVs affecting genes, mutated in at least one primary sample (including [5])
and that were damaging according to three functional predictors (see Figure 1). N: not detected;
W, K, S, M, Y, R: indicate heterozygous mutations. Numbers of normal and mutant reads are
provided in column AE-AG. If the same mutation was found in 2 or 3 cases, two or 3 values are
provided.
S_Table 6: Most frequent mutations in MM. Genes mutated in at least four primary MM
samples (incl. [5]) and at least one cell line and that passed the thresholds for at least two
functional predictors in at least one of our samples. All mutations were validated by Sanger
sequencing in the respective cell lines and our primary MM sample.
S_Table 7: 137 SNVs found to affect genes in at least one primary MM sample and that were
damaging according to three functional predictors (see Figure 1). N: not detected; W, K, S, M,
Y, R: heterozygous mutations. Numbers of normal and mutant reads are provided in column
AE- AG. If the same mutation was found in 2 or 3 cases, two or 3 values are provided.
S_Table 8: GSEA pathway annotation. 50 most significant gene sets. 79 genes, mutated in at
least one of the five primary MM (Figure 1) were annotated to pathways using the C2-collection
of the GSEA annotation database. red label: growth factor receptor signaling; yellow: adhesion
associated pathway.
S_Table 9 A: 20 most significant gene sets. 193 genes, mutated in at least one of the five
primary MM and/or at least one of the 38 primary MM [5] + minimum one of the six cell lines
(Figure 1), were annotated to pathways using the C2-collection of the GSEA annotation
database. yellow: adhesion associated pathways. red: growth factor receptor associated
pathways
S_Table 9 B: 50 most significant gene sets. 193 genes, mutated in at least one of the five
primary MM and/or at least one of the 38 primary MM [5] + minimum one of the six cell lines
(Figure 1), were annotated to pathways using the C2-collection of the GSEA annotation
database. yellow: adhesion associated pathways. red: growth factor receptor associated
pathways.
S_Table 10: GSEA pathway annotation. 50 most significant gene sets. 1,429 genes, mutated
in the 38 primary MM published by Chapman et al. [5] were annotated to pathways using the
C2-collection of the GSEA annotation database. Yellow: adhesion associated gene sets, blue:
gene sets associated with histone modification.
S_Table 11 A+B: (A) List of RTKs. (B) List of adhesion molecules. Please note that some
molecules may occure more than once, because they might belong to more than one group of
adhesion molecules.
S_Table 12: Information on which mutated gene (labeled with asteriks in Fig.3) was identified in
which cell line. Red (bold): Mutated in at least one primary MM (including 5) and “damaging”
according to three functional predictors. Red: Mutated in one of the 43 primary MM (including 5).
Black (bold): Mutated in a cell line and “damaging” according to three functional predictors.
Black: Mutated in at least one cell line. n.d.: not done, n.e.: not evaluable
S_Table 13: Mutation profile of 36/38 primary MM samples ([5]) with respect to adhesion
molecule- and RTK-signaling. Genes are listed that were mutated in at least one cell line and at
least one primary MM ([5]). All mutations mentioned (x: mutated, xx: mutated twice in the same
sample, homoz.: homozygous) were damaging in at least two functional predictors if not
otherwise specified (<2=less than 2 predictors). Genes that belonged to the same signaling
network were highlighted in yellow (bright: medium confidence, light: low confidence).
S_Table 14: Mutation details for genes listed in Table 2 and S_Table 12. N: not detected; W, K,
S, M, Y, R: heterozygous mutations. Numbers of normal and mutant reads are provided in
columns AE-AG. If the same mutation was found in 2 or 3 cases, two or 3 values are provided.
Figure Legends (S_Figures)
S_Figure 1: Protein Domains of NTRK2 according to the graphical view of the Nucleotide
database of NCBI. Arrows indicate the mutation sites. The mutation in the immunoglobulin
domain occurred in the MM cell line L363 and the mutation in the tyrosine kinase domain in a
primary MM sample. SP= prediction SignalP, LRRNT=Leucine rich repeat N-terminal domain,
LRR=Leucine rich repeat, LRRCT=Leucine rich repeat C-terminal domain, IG=Immunoglobulin
domain, Ig_TrkB-d5=Fifth domain (immunoglobulin-like) of Trk receptor TrkB, TMR=
transmembranregion, SHC=interaction with, SHC1P=Phosphorylation, PTKc_TrkB=Catalytic
domain of the Protein Tyrosine, Kinase, Tropomyosin Related Kinase B