Supplemental Table 1. List of genes with CNAs in CRC annotated with associated signaling
pathways, clinicopathological features and therapeutic strategies.
Chromosome
Gene
chr1
PRKAB2
chr1
CNA
Signaling pathway
Relevance to disease
features
As therapeutic target
Loss
Controls AMPK under p53
regulation
-
-
S100A2
Loss
Calcium-binding protein,
promotes p53 function
-
-
chr2
ALK
Gain
Receptor tyrosine kinase
pathway
Independent prognostic
marker for poor survival
in CRC across all stages
ALK inhibitor under test
for treating lung cancer
and other cancers
chr2
BUB1
Gain
Spindle assembly
checkpoint
-
-
chr3
FHIT
Gain
Apoptotic regulator
Progression to higher
cancer stage
-
chr4
FBXW7
Loss
Tumor suppressor that
controls cell cycle and
ubiquitinates c-Myc and
cyclin E
Independent prognostic
factor for survival
-
chr4
UGT2B28
Loss
Regulates metabolism of
steroids
-
-
chr4
SULT1B1
Loss
Catalyze the sulfate
conjugation of many
hormones
Related to tissue
dedifferentiation
-
chr4
CXCL6
Loss
Chemoattraction,
inflammatory responses,
tumor growth and
angiogenesis
Correlated with the
invasiveness ofCRC
-
chr4
EIF4E
Loss
Translation initiation factor
involved in directing
ribosomes to the cap
structure of mRNAs
-
-
chr5
JS-2
(FAM173B)
Gain
A single-pass membrane
protein with unkonwn
function
Related to pathological
subtypes and staging
-
chr6
TNFAIP3
Gan
Tumor growth and
progression depend on
the activation of nuclear
factor-kappaB (NFκB)
Prognostic marker in
patients with advanced
stages of CRC
-
chr7
EGFR
Gain
involved in cell
proliferation with
antiapoptotic properties
Poor outcome and
metastasis
The anti-EGFR
monoclonal antibodies
display effects in treating
advanced colorectal
cancer
chr7
CYP3A5
CYP3A57
Gain
The P450 enzymes,
involved the metabolism
of anti-cancer drugs
Poor outcome and
metastasis
Proposed for guiding
anti-cancer drug selection
chr7
PODXL
Gain
cell adhesion,metastatic
process
Poor prognosis
-
chr7
RAPGEF5
Gain
serves as a RAS activator
by promoting
the acquisition of GTP
-
-
chr7
WNT2
Gain
Promotes Wnt/β-Catenin
pathway
Contributes to initiation
and progression of CRC
Flavonoids proposed for
treating CRCs with
activated Wnt signaling
chr7
MET
Gain
A growth factor receptor
that promotes tumor
growth, angiogenesis and
metastasis
Associates with
invasivion and
metastasis
MET inhibitors such as
ARQ197 under clinical
trial for treating CRC,
other inhibitors such as
tivantinib, onartuzumab,
and cabozantinib for
treating other cancers
chr8
MYC
Gain
Crucial oncogene that
regulates transactivation
of many cancer-related
genes
Overexpression
associates with
improved 5-year survival
Myc inhibitors are studied
in vitro and in animal
models
chr8
PPP2CB
Loss
A Ser/Thr phosphatases
in negative control of cell
growth and division
-
-
chr8
MTUS1
Loss
A tumor suppressor
involved in AT2 signaling
pathways
Downregulation
associates with poor
overall and disease-free
survival
-
chr8
CSMD1
Loss
A potential tumor
suppressor with deletions
promoting cancer
aggressiveness
Associates with poor
prognosis of CRC
-
chr10
CASP7
Loss
apoptosis effector
caspase gene
-
-
chr10
PTEN
Loss
Tumor suppressor in
regulation of the
PI3K-Akt-mTOR pathway
Not a predictive factor
for anti-VEGF therapy in
mCRC.
-
chr11
IGF2
Gain
PI3K pathway
-
-
chr11
miR-483
Gain
May suppresses the
expression of
DPC4/Smad4
-
-
chr11
91H (antisense
RNA of H19)
Gain
(TCGA)
LncRNA, upregulation of
IGF2 expression
development and
progression of CRC
poorer prognosis
chr12
WNK1
Gain
a member of the WNK
family of
serine/threonine kinases
which affect MAPK
signaling
evasion of apoptosis,
invasion and metastasis,
and metabolic
adaptation
-
chr12
ARHGDIB
Loss
Regulates COX2 and
inhibit RhoGTPase, which
inhibits cancer invasion
Associates with distant
metastasis of CRC
-
chr12
KRAS
Gain
Oncogene, a small
GTPase with malignant
transforming function in
multiple tumors
KRAS CNA associates
with responses to
anti-EGFR therapy
Proposed inhibition of
KRAS signal by MEK1/2
inhibitors
chr12
RERGL
Gain
Ras-Related And
Estrogen-Regulated
Growth Inhibitor-Like
Protein
-
-
chr13
GPC5
Gain
Glypican-related integral
membrane proteoglycan,
control of cell division and
growth regulation
Associates with tumor
recurrence and shorter
disease-free survival
-
chr13
IRS2
Gain
IGF2–IGF1R–IRS2 axis
signals to PI3K
-
-
chr15
BLM
Loss
RecQ helicase family
-
-
chr16
WWOX
Loss
WNT/betacatenin pathway
tumor suppressor
-
chr16
AXIN1
Loss
Induce apoptosis
prognostic
-
chr17
ERBB2 (HER2)
Gain
Receptor tyrosine-protein
kinase regulating MAPK,
PI3K/Akt, PKC, STAT
signals
Overexpression is not a
predictor of outcome but
may indicate respond to
Herceptin therapy
anti-ERBB2 antibody
trastuzumab
chr17
TP53
Loss
Tumor suppressor as a
master regulator of cell
apoptosis
Loss of TP53 gene may
associate with CRC
outcome
MDM2 inhibitor proposed
for treating tumors with
loss of p53
chr17
WDR16
Loss
signaltransduction, RNA
processing, cytoskeleton
remodeling, the regulation
of vesicular traffic, and cell
division
involved in
tumorigenesis,
-
chr18
DCC
Loss
A cell adhesion protein
partially localized in lipid
rafts, involved in induction
of apoptosis without ligand
genetic biomarkers of
sCRC and typicallyare
associated with
advanced disease
-
chr18
SMAD4
Loss
Regulates the
transcription of target
genes in TGF-β pathway
An independent
diagnostic biomarker for
CRC
-
chr18
CABLES1
Loss
Catalyze tyrosine
phosphorylation of
cyclin-dependent kinases
CABLES1-deficient mice
had more DMH-induced
tumors and shorter
survival
-
chr18
DNAM-1
Loss
Suppressor of cytokine
signaling 6 (SOCS6)and
a-7 nictonic
receptor(ACHR-7)
Worse prognosis among
patients with sporadic
CRC
-
chr18
BRUNOL4
Loss
Regulates pre-mRNA
alternative splicing, mRNA
editing, and translation
Independent adverse
prognostic factor
-
chr18
PHLPP1
Loss
Negative regulator of Akt
-
therapeutic or diagnostic
tool
chr18
RALBP1
Loss
Anti-apoptosis function
and protection from stress
by glutathione conjugation
-
transportation of chemical
anti-cancer compounds
chr18
TYMS
Loss
Maintains the dTMP pool
critical for DNA replication
and repair
Overexpression
associates with poorer
overall survival in CRC
Target for the anti-cancer
drug 5-fluorouracil (5-FU)
chr18
MAPRE2,
ZNF24,
DNAM-1,
SOCS6,
ACHR-7,
CCDC68,
TCF4, RAX
Loss
Transcription factor
activity and DNA binding
(DAVID annotation)
Associates with
metastasis and shorter
overall survival in CRC
-
chr19
LTBP4
Gain
TGFβ-pathway, prevent
tumor suppressive
downstream reactions
such as apoptosis, and
growth arrest
chr19
BAX
Loss
pro-apoptotic gene
Associates with shorter
disease-free survival in
CRC
5-FU-based treatment
resistance
chr19
POLD1
-
impaired DNA replication
generating breaks
-
-
chr20
BCL2L1
Gain
Mitochondrial pathway of
apoptosis
Increased BCL2L1
expression indicates
poor prognosis in CRC
overexpression of
BCL2L1 associates with
chemotherapy resistance
chr20
POFUT1
Gain
Addition of O-linked
fucose to the EGF
domains of the Notch
receptor
-
-
chr20
SNAI1
Gain
through Axin and
GSK-3beta for
degradation of
beta-catenin in
proteasomes in the
Wnt-signaling pathway
-
-
chr20
AURKA
Gain
Phosphorylates TP53 and
regulates cell proliferation
-
-
chr20
WISP2
Gain
Transforming growth
factor signaling pathway
-
-
chr20
CDC25B
Gain
Proceed through the
S-phase checkpoint and
prematurelyenter mitosis
-
-
chr20
AHCY
Gain
MYC-target gene
-
-
-
chr20
PCNA
Gain
DNA synthesis and cell
cycle progression
-
PCNA inhibitors under
study in vitro
chr20
RPN2
Gain
Inhibits Bcl-mediated
apoptosis
-
-
chr20
TH1L
Gain
Belongs to negative
elongation factor complex
-
-
chr20
PRPF6
Gain
Maintaining cell viability
-
-
chr20
SNAI1
Gain
Cell adhesion
Wnt-signaling
-
-
chr20
BMP7
Gain
Transforming growth
factor pathway
Independent prognostic
factor of liver metastasis
and overall survival
-
chr20
TOP1
Gain
Catalyzes the unwinding
of DNA and creates
single-strand molecules
Associates with CRC
stage
-
chr20
PLCG1
Gain
Response to growth factor
stimulation and regulates
cell invasion and
metastasis
-
-
chr20
PTPRT
Gain
Regulation of cell
adhesion
-
-
chr20
EEF1A2
Gain
Encodes a subunit of the
elongation factor-1
complex
Prognostic of a poor
response to taxol
-
chr22
ApoL6
Loss
With BH3 domain,
regulation of mitochondrial
apoptosis
-
proposing a new strategy
for chemotherapy
SEX
X,Y, multiple
genes
Gain
(X),
Loss (Y)
"Feminization" associates
with microsatellite stability
and BRAF status
No significant
association with
clinicopathological
features including
disease-free survival
-
mtDNA
Multiple genes
Gain,
loss
Cell metabolism and ATP
generation
Gain in early stage
tumors, and loss in
invasive tumors
Proposed as biomarker in
early diagnosis of CRC
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Supplementary Table 1 (docx 31K)