Download Gene Section FGFR4 (fibroblast growth factor receptor 4) in Oncology and Haematology

Atlas of Genetics and Cytogenetics
in Oncology and Haematology
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Gene Section
Review
FGFR4 (fibroblast growth factor receptor 4)
Alberto Peláez-García, Rodrigo Barderas, J Ignacio Casal
Functional Proteomics Laboratory, Centro de Investigaciones Biologicas (CIB-CSIC), 28040 Madrid, Spain
(APG, JIC), Departamento Bioquimica y Biologia Molecular I, Universidad Complutense de Madrid, 28040
Madrid, Spain (RB)
Published in Atlas Database: May 2012
Online updated version : http://AtlasGeneticsOncology.org/Genes/FGFR4ID512ch5q35.html
DOI: 10.4267/2042/48227
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2012 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Identity
DNA/RNA
Other names:
CD334, JTK2, TKF
HGNC (Hugo):
FGFR4
Location:
5q35.2
Description
The DNA was cloned in 1991 (Partanen et al.,
1991). 18.9 kb; 18 exons.
Transcription
3.1 kb mRNA; alternative splicing gives rise to 18
transcripts with evidence of 11 transcripts at protein
level.
FGFR4 comprises an extracellular domain, a transmembrane domain, and an intracellular domain. FGFR4 alternative splicing has been
described, with up to 18 different transcripts ranging from 552 to 3559 bp, (evidence of 11 transcripts at protein level ranging from 87 to
1030 aminoacids).
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FGFR4 (fibroblast growth factor receptor 4)
Peláez-García A, et al.
Analysis of the expression of FGFR4 in SW480 colorectal cancer cells by Confocal Microscopy. FGFR4 was detected in plasma
membrane, cytoplasm and nucleus. The 4',6-diamidino-2-phenylindole (DAPI) was used to detect the nucleus of the cells in blue.
Representative micrographs show FGFR4 in green and F-actin (TRITC-phalloidin) in red.
lamina propria, liver, lung, lymph node, mammary
gland, muscle, muscularis mucosa, ovary, pituitary
gland, renal tubular epithelium, retina, skin, spleen,
stomach, sublingual gland, ureter, urothelium and
uterus (www.hprd.org).
Protein
Description
The canonical sequence possesses 802 amino acids,
120 kDa, contains a signal peptide 1-17 amino acids, an
extracellular domain with 3 Ig-like loops, a
transmembrane domain with 26 amino acids and an
intracellular domain with tyrosine kinase activity.
Transcripts lacking the intracellular domain and
transmembrane domain are secreted.
Localisation
Plasma membrane, but also some FGF-FGFR
complexed are endocytosed and develop its function
directly in the cytosol or nucleus.
FGFR4 isoform 2 may be secreted.
Expression
Function
FGFR4 is expressed in a tissue-specific manner during
embryogenesis and displays unique affinity for certain
FGF ligands (FGF1, FGF2, FGF4, FGF6, FGF8, FGF9,
FGF16, FGF17, FGF18 and FGF19). FGFR4 function
is not essential during embryogenesis and adult life
(Weinstein et al., 1998), though it may be involved in
several metabolic pathways (Gutierrez et al., 2006; Yu
et al., 2000).
Evidence of FGFR4 expression has been described at:
adrenal cortex, adrenal gland, bile duct, cervix, cornea,
corneal endothelial cell, corneal epithelial cell, heart,
hepatocyte, intestine, islets of langerhans, kidney,
FGF receptor with tyrosine-protein kinase activity acts
as cell-surface receptor for fibroblast growth factors
and plays a role in the regulation of cell proliferation,
differentiation and migration. Binding of fibroblast
growth factors produces receptor dimerization,
autophosphorilation and signal transduction.
FGFR4 binds mainly FGF19. There are evidences that
FGFR4 function may not necessarily require FGF
ligand: i) heparin in the absence of FGF produced the
activation of FGFR4 (Gao and Goldfarb, 1995), ii)
FGFR4 was found to function in a complex with NCAM independently of FGF (Cavallaro et al., 2001),
and iii) the detection of N-linked glycosylation on an
Atlas Genet Cytogenet Oncol Haematol. 2012; 16(11)
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FGFR4 (fibroblast growth factor receptor 4)
Peláez-García A, et al.
overexpressed extracellular domain of human FGFR4
suggested that the function of this receptor might also
be regulated by glycosylation, similar to what occurs
with other FGFRs (Tuominen et al., 2001).
A key regulator of the FGFR4 pathway is its coreceptor klotho-beta (KLB), a 130 kDa transmembrane
protein that exhibits a more restricted expression
profile in adipose, liver and pancreas tissues. KLB and
FGFR4 are both expressed at high levels in mature
hepatocytes, where KLB stabilizes FGF19-FGFR4
binding to regulate production of cholesterol 7ahydroxylase (CYP7A1) and hepatocyte proliferation
(Kurosu et al., 2007; Lin et al., 2007; Wu et al., 2010).
It has also been identified that FGFR4 is part of a
complex with MT1-MMP, where MT1-MMP and
FGFR4 are regulated in an opposite direction
depending on the tumor progression and the presence
of FGFR4 SNP Gly388Arg (Hotary et al., 2000; Lehti
et al., 2000; Okada et al., 1995; Sugiyama et al., 2010).
This SNP changes Gly388Arg in the predicted FGFR4
transmembrane domain, resulting in enhanced stability
of the activated receptor (Ingvarsen et al., 2008). Both
FGFR4-R388 and FGFR4-G388 form a complex with
MT1-MMP and induced MT1-MMP tyrosil
phosphorylation, but they had opposite effects on MT1MMP levels. FGFR4-R388 stabilizes MT1-MMP,
whereas FGFR4-G388 down-regulates MT1-MMP.
The Y573F point mutation blocks MT1-MMP tyrosyl
phosphorylation increasing cell-membrane MT1-MMP
(Ingvarsen et al., 2008).
Homology
Other fibroblast growth factor receptors (FGFR1,
FGFR2 and FGFR3).
Homology with other tyrosin-protein kinase family
members through its tyrosin-protein kinase domain.
Mutations
Germinal
In the FGFR4 gene transcript from a mammary
carcinoma cell line, a G-to-A transition was discovered
that resulted in the substitution of glycine by arginine at
position 388 in the transmembrane domain of the
receptor (Bange et al., 2002). The arg388 allele was
also found in cell lines derived from a variety of other
tumor types as well as in the germline of cancer
patients and healthy individuals. Analysis of 3
geographically separated groups indicated that it occurs
in approximately 50% of humans. Moreover, the
FGFR4 arg388 allele was associated with early
metastasis and advanced tumor-node metastasis stage
in 82 colon cancer patients.
The results support that FGFR4 arg388 allele
represents an innocuous determinant in healthy
individuals but predisposes cancer patients for
significantly accelerated disease progression.
FGFR4 related pathways are mostly related to an enhanced proliferation, cell survival and cell migration in cancer.
Atlas Genet Cytogenet Oncol Haematol. 2012; 16(11)
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FGFR4 (fibroblast growth factor receptor 4)
Peláez-García A, et al.
Mutational spectrum of the human FGFR4 gene. Red labels represent somatic mutations occurring in different cancers. Black labels
represent germinal mutations.
Four of the mutations affected residues Asn535 and
Val550 and were predicted to be activating mutations
that would alter conformational dynamics during
phosphorylation in the case of Asn535 substitutions
and ATP binding in the case of Val550 substitutions.
Using human and mouse rhabdomyosarcoma cell
lines, it was found that two of these mutations,
Asn535Lys (N535K) and Val550Glu (V550E),
increased autophosphorylation, Stat3 signaling, cell
growth, tumor proliferation and metastatic potential
when injected into nude mice (Taylor et al., 2009).
Somatic
FGFR4
was
significantly
overexpressed
in
rhabdomyosarcoma tumors of high metastatic potential.
Higher FGFR4 expression was associated to a lower
rate of survival (Taylor et al., 2009).
Six missense mutations were observed in the FGFR4
tyrosine kinase domain among 7 of 94 (7.5%) primary
rhabdomyosarcomas, and none of these substitutions
were found in normal controls. Comparison with the
available genomic data suggested that the mutations
were somatic.
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FGFR4 (fibroblast growth factor receptor 4)
Peláez-García A, et al.
association between the presence of the SNP and
predisposition to develop skin cancer.
These mutants differentiated mouse NIH3T3 cells to an
enhanced metastatic phenotype.
Ruhe et al. discovered the Y367C mutation in the
FGFR4 gene by a comprehensive analysis of the
tyrosine kinase gene family in cancer cell lines (Ruhe
et al., 2007).
This mutation occurred in the MDA-MB453 breast
cancer cell line.
Cloning and ectopic expression of the FGFR4 Y367C
mutant in HEK293 cells revealed high pERK levels and
enhanced cell proliferation (Roidl et al., 2010).
Based on these findings, it has been proposed that
FGFR4 may be a driver gene of tumour growth.
Hepatocellular carcinoma
Note
FGF19 and its receptor FGFR4 are co-expressed in
human liver, lung and colon tumors and in several
colon cancer cell lines.
Prognosis
The presence of the SNP in cancer patients in a
population of 58 cases (29% heterozygous and 24%
homozygous) and 88 controls (43% heterozygous
and 27% homozygous) was associated with a poor
prognosis in hepatocellular carcinoma patients.
Moreover, overexpression of FGFR4 was also observed
in 33% of cancer patients (Ho et al., 2009).
Oncogenesis
A specific antibody directed against FGF19 abolished
signaling mediated through FGFR4 in vitro, resulting in
an inhibition of tumor xenografts in vivo and
preventing hepatocellular carcinomas in FGF19
transgenic mice.
The targeting of FGF19 by antibodies that disrupt
FGF19-FGFR4 interaction could be beneficial for
colon, liver and lung cancer patients whose tumors coexpress FGF19 and FGFR4 (Desnoyers et al., 2008).
Implicated in
Various cancers
Note
Gly388Arg polymorphism
Disease
Gly388Arg polymorphism seems to be associated to
poor prognosis and cancer aggressiveness in different
cancers but no with predisposition to any cancer as it
has been described prostate, breast, gastric and skin
cancer (see in paragraphs below).
Prognosis
Gly388Arg seems to be associated to a worst prognosis
and aggressiveness in different cancers. The SNP might
be mainly associated with increased risks of breast and
prostate cancer, and contributes to susceptibility to
cancer, especially in Asians (Xu et al., 2010).
Breast cancer
Disease
Approximately 40% and 10% of breast cancer patients
present the Gly388Arg polymorphism in heterozygous
or homozygous, respectively; without significant
differences in the presence of the SNP between control
and case specimens. FGFR4 expression levels do not
correlate with the presence of the SNP (Thussbas et al.,
2006).
Gly388Arg polymorphism is not associated with
initiation of breast cancer but has been suggested that
could be a marker for increased tumor aggressiveness
in advanced breast cancer (Bange et al., 2002; Jezequel
et al., 2004; Thussbas et al., 2006).
Prostate cancer
Disease
It has been described a significant association between
FGFR4 polymorphism and prostate cancer using a total
of 2618 cases and 2305 controls. FGFR4 contributes to
susceptibility to prostate cancer (Liwei et al., 2011).
FGFR4 polymorphism results in an increased stability
and activation of the receptor, resulting in an
association of prostate cancer patients to clinical
progression (Wang et al., 2008).
Gastric cancer
Melanoma
Note
FGFR4
expression
abundance
by
immunohistochemistry was intermediate or high in
41% and 38% of gastric cancer tissue samples.
Disease
The SNP is present in 50% of gastric cancer patients in
either heterozygous or homozygous.
It was found a significant association between
Gly388Arg and gastric cancer patient survival,
suggesting that FGFR4 Arg388 genotype might be a
marker of gastric cancer progression (Ye et al., 2010;
Ye et al., 2011).
Oncogenesis
FGFR4 expression was associated to lymph node status
and survival decreased with an increased in FGFR4
Disease
FGFR4 Arg388 polymorphism was detected in 83 out
of 185 (45%) melanoma patients and was significantly
associated to tumour thickness and the nodular
melanoma subtype.
Moreover, the analysis of 137 melanoma tissues by
immunohistochemistry showed that 45% of the
specimens expressed FGFR4 at different levels and
correlated with pTNM tumour stages, metastases,
number of primary tumors and survival (Streit et al.,
2006).
In another independent study with 218 samples from
melanoma, 285 squamous cell carcinoma, 300 basal
cell carcinoma and 870 controls, it was observed no
Atlas Genet Cytogenet Oncol Haematol. 2012; 16(11)
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FGFR4 (fibroblast growth factor receptor 4)
Peláez-García A, et al.
I collagen matrix by membrane-type matrix metalloproteinases
1, 2, and 3. J Cell Biol. 2000 Jun 12;149(6):1309-23
expression. Knockdown of FGFR4 expression
produced a decrease in proliferation by increasing the
apoptosis rate of gastric cancer cell lines in vitro (Ye et
al., 2011).
Lehti K, Valtanen H, Wickström SA, Lohi J, Keski-Oja J.
Regulation of membrane-type-1 matrix metalloproteinase
activity by its cytoplasmic domain. J Biol Chem. 2000 May
19;275(20):15006-13
Rhabdomyosarcomas
Note
Rhabdomyosarcoma is a cancer that takes place in the
childhood and is originated from skeletal muscle.
Oncogenesis
FGFR4 is highly overexpressed in RMS samples at
mRNA and protein level in comparison to pediatric
tumors and normal tissue (Taylor et al., 2009). FGFR4
overexpression has been linked to advanced-stage
cancer and poor survival (Baird et al., 2005; Taylor et
al., 2009). FGFR4 silencing in the RH30 alveolar RMS
human cell line produced a significant reduction in
tumor
growth
and
lung
metastases
when
xenotransplanted in mice (Taylor et al., 2009).
Yu C, Wang F, Kan M, Jin C, Jones RB, Weinstein M, Deng
CX, McKeehan WL. Elevated cholesterol metabolism and bile
acid synthesis in mice lacking membrane tyrosine kinase
receptor FGFR4. J Biol Chem. 2000 May 19;275(20):15482-9
Cavallaro U, Niedermeyer J, Fuxa M, Christofori G. N-CAM
modulates tumour-cell adhesion to matrix by inducing FGFreceptor signalling. Nat Cell Biol. 2001 Jul;3(7):650-7
Tuominen H, Heikinheimo P, Loo BM, Kataja K, Oker-Blom C,
Uutela M, Jalkanen M, Goldman A. Expression and
glycosylation studies of human FGF receptor 4. Protein Expr
Purif. 2001 Mar;21(2):275-85
Bange J, Prechtl D, Cheburkin Y, Specht K, Harbeck N,
Schmitt M, Knyazeva T, Müller S, Gärtner S, Sures I, Wang H,
Imyanitov E, Häring HU, Knayzev P, Iacobelli S, Höfler H,
Ullrich A. Cancer progression and tumor cell motility are
associated with the FGFR4 Arg(388) allele. Cancer Res. 2002
Feb 1;62(3):840-7
Colorectal cancer
Note
FGFR4 is overexpressed in low- and high-metastatic
CRC cell lines, with higher expression at late CRC
stages (Barderas et al., 2012).
FGFR4 is a tumor-associated antigen of autoantibodies
in colorectal cancer patients; it might serve for the
diagnosis of colorectal cancer at early stages in
combination with other tumor-associated antigens
(Babel et al., 2009; Barderas et al., 2012).
Shah RN, Ibbitt JC, Alitalo K, Hurst HC. FGFR4
overexpression in pancreatic cancer is mediated by an intronic
enhancer activated by HNF1alpha. Oncogene. 2002 Nov
28;21(54):8251-61
Jézéquel P, Campion L, Joalland MP, Millour M, Dravet F,
Classe JM, Delecroix V, Deporte R, Fumoleau P, Ricolleau G.
G388R mutation of the FGFR4 gene is not relevant to breast
cancer prognosis. Br J Cancer. 2004 Jan 12;90(1):189-93
Baird K, Davis S, Antonescu CR, Harper UL, Walker RL, Chen
Y, Glatfelter AA, Duray PH, Meltzer PS. Gene expression
profiling of human sarcomas: insights into sarcoma biology.
Cancer Res. 2005 Oct 15;65(20):9226-35
Pancreatic cancer
Oncogenesis
FGFR4 is overexpressed in 50-70% of pancreatic
cancer cell lines and pancreatic carcinomas (Motoda et
al., 2011; Shah et al., 2002).
FGFR4 is significantly increased in high-grade
pancreatic intraepithelial neoplasia and pancreatic
ductal adenocarcinoma, where FGFR4 stimulation by
FGF19 increased cell adhesion to extracellular matrix
and decreased cell migration.
Gutierrez A, Ratliff EP, Andres AM, Huang X, McKeehan WL,
Davis RA. Bile acids decrease hepatic paraoxonase 1
expression and plasma high-density lipoprotein levels via FXRmediated signaling of FGFR4. Arterioscler Thromb Vasc Biol.
2006 Feb;26(2):301-6
Streit S, Mestel DS, Schmidt M, Ullrich A, Berking C. FGFR4
Arg388 allele correlates with tumour thickness and FGFR4
protein expression with survival of melanoma patients. Br J
Cancer. 2006 Jun 19;94(12):1879-86
Thussbas C, Nahrig J, Streit S, Bange J, Kriner M, Kates R,
Ulm K, Kiechle M, Hoefler H, Ullrich A, Harbeck N. FGFR4
Arg388 allele is associated with resistance to adjuvant therapy
in primary breast cancer. J Clin Oncol. 2006 Aug
10;24(23):3747-55
References
Partanen J, Mäkelä TP, Eerola E, Korhonen J, Hirvonen H,
Claesson-Welsh L, Alitalo K. FGFR-4, a novel acidic fibroblast
growth factor receptor with a distinct expression pattern.
EMBO J. 1991 Jun;10(6):1347-54
Kurosu H, Choi M, Ogawa Y, Dickson AS, Goetz R,
Eliseenkova AV, Mohammadi M, Rosenblatt KP, Kliewer SA,
Kuro-o M. Tissue-specific expression of betaKlotho and
fibroblast growth factor (FGF) receptor isoforms determines
metabolic activity of FGF19 and FGF21. J Biol Chem. 2007
Sep 14;282(37):26687-95
Gao G, Goldfarb M. Heparin can activate a receptor tyrosine
kinase. EMBO J. 1995 May 15;14(10):2183-90
Okada A, Bellocq JP, Rouyer N, Chenard MP, Rio MC,
Chambon
P,
Basset
P.
Membrane-type
matrix
metalloproteinase (MT-MMP) gene is expressed in stromal
cells of human colon, breast, and head and neck carcinomas.
Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2730-4
Lin BC, Wang M, Blackmore C, Desnoyers LR. Liver-specific
activities of FGF19 require Klotho beta. J Biol Chem. 2007 Sep
14;282(37):27277-84
Ruhe JE, Streit S, Hart S, Wong CH, Specht K, Knyazev P,
Knyazeva T, Tay LS, Loo HL, Foo P, Wong W, Pok S, Lim SJ,
Ong H, Luo M, Ho HK, Peng K, Lee TC, Bezler M, Mann C,
Gaertner S, Hoefler H, Iacobelli S, Peter S, Tay A, Brenner S,
Venkatesh B, Ullrich A. Genetic alterations in the tyrosine
Weinstein M, Xu X, Ohyama K, Deng CX. FGFR-3 and FGFR4 function cooperatively to direct alveogenesis in the murine
lung. Development. 1998 Sep;125(18):3615-23
Hotary K, Allen E, Punturieri A, Yana I, Weiss SJ. Regulation
of cell invasion and morphogenesis in a three-dimensional type
Atlas Genet Cytogenet Oncol Haematol. 2012; 16(11)
807
FGFR4 (fibroblast growth factor receptor 4)
Peláez-García A, et al.
kinase transcriptome of human cancer cell lines. Cancer Res.
2007 Dec 1;67(23):11368-76
receptor 4 regulates tumor invasion by coupling fibroblast
growth factor signaling to extracellular matrix degradation.
Cancer Res. 2010 Oct 15;70(20):7851-61
Desnoyers LR, Pai R, Ferrando RE, Hötzel K, Le T, Ross J,
Carano R, D'Souza A, Qing J, Mohtashemi I, Ashkenazi A,
French DM. Targeting FGF19 inhibits tumor growth in colon
cancer xenograft and FGF19 transgenic hepatocellular
carcinoma models. Oncogene. 2008 Jan 3;27(1):85-97
Wu X, Ge H, Lemon B, Vonderfecht S, Weiszmann J, Hecht R,
Gupte J, Hager T, Wang Z, Lindberg R, Li Y. FGF19-induced
hepatocyte proliferation is mediated through FGFR4 activation.
J Biol Chem. 2010 Feb 19;285(8):5165-70
Ingvarsen S, Madsen DH, Hillig T, Lund LR, Holmbeck K,
Behrendt N, Engelholm LH. Dimerization of endogenous MT1MMP is a regulatory step in the activation of the 72-kDa
gelatinase MMP-2 on fibroblasts and fibrosarcoma cells. Biol
Chem. 2008 Jul;389(7):943-53
Xu W, Li Y, Wang X, Chen B, Wang Y, Liu S, Xu J, Zhao W,
Wu J. FGFR4 transmembrane domain polymorphism and
cancer risk: a meta-analysis including 8555 subjects. Eur J
Cancer. 2010 Dec;46(18):3332-8
Ye Y, Shi Y, Zhou Y, Du C, Wang C, Zhan H, Zheng B, Cao X,
Sun MH, Fu H. The fibroblast growth factor receptor-4 Arg388
allele is associated with gastric cancer progression. Ann Surg
Oncol. 2010 Dec;17(12):3354-61
Wang J, Yu W, Cai Y, Ren C, Ittmann MM. Altered fibroblast
growth factor receptor 4 stability promotes prostate cancer
progression. Neoplasia. 2008 Aug;10(8):847-56
Babel I, Barderas R, Díaz-Uriarte R, Martínez-Torrecuadrada
JL, Sánchez-Carbayo M, Casal JI. Identification of tumorassociated autoantigens for the diagnosis of colorectal cancer
in serum using high density protein microarrays. Mol Cell
Proteomics. 2009 Oct;8(10):2382-95
Liwei L, Chunyu L, Jie L, Ruifa H. Association between
fibroblast growth factor receptor-4 gene polymorphism and risk
of prostate cancer: a meta-analysis. Urol Int. 2011;87(2):15964
Motoda N, Matsuda Y, Onda M, Ishiwata T, Uchida E, Naito Z.
Overexpression of fibroblast growth factor receptor 4 in highgrade pancreatic intraepithelial neoplasia and pancreatic ductal
adenocarcinoma. Int J Oncol. 2011 Jan;38(1):133-43
Ho HK, Pok S, Streit S, Ruhe JE, Hart S, Lim KS, Loo HL,
Aung MO, Lim SG, Ullrich A. Fibroblast growth factor receptor
4 regulates proliferation, anti-apoptosis and alpha-fetoprotein
secretion during hepatocellular carcinoma progression and
represents a potential target for therapeutic intervention. J
Hepatol. 2009 Jan;50(1):118-27
Ye YW, Zhou Y, Yuan L, Wang CM, Du CY, Zhou XY, Zheng
BQ, Cao X, Sun MH, Fu H, Shi YQ. Fibroblast growth factor
receptor 4 regulates proliferation and antiapoptosis during
gastric cancer progression. Cancer. 2011 Dec 1;117(23):530413
Taylor JG 6th, Cheuk AT, Tsang PS, Chung JY, Song YK,
Desai K, Yu Y, Chen QR, Shah K, Youngblood V, Fang J, Kim
SY, Yeung C, Helman LJ, Mendoza A, Ngo V, Staudt LM, Wei
JS, Khanna C, Catchpoole D, Qualman SJ, Hewitt SM, Merlino
G, Chanock SJ, Khan J. Identification of FGFR4-activating
mutations in human rhabdomyosarcomas that promote
metastasis in xenotransplanted models. J Clin Invest. 2009
Nov;119(11):3395-407
Barderas R, Babel I, Díaz-Uriarte R, Moreno V, Suárez A,
Bonilla F, Villar-Vázquez R, Capellá G, Casal JI. An optimized
predictor panel for colorectal cancer diagnosis based on the
combination of tumor-associated antigens obtained from
protein and phage microarrays. J Proteomics. 2012 Aug
3;75(15):4647-55
Roidl A, Foo P, Wong W, Mann C, Bechtold S, Berger HJ,
Streit S, Ruhe JE, Hart S, Ullrich A, Ho HK. The FGFR4
Y367C mutant is a dominant oncogene in MDA-MB453 breast
cancer cells. Oncogene. 2010 Mar 11;29(10):1543-52
This article should be referenced as such:
Peláez-García A, Barderas R, Casal JI. FGFR4 (fibroblast
growth factor receptor 4). Atlas Genet Cytogenet Oncol
Haematol. 2012; 16(11):802-808.
Sugiyama N, Varjosalo M, Meller P, Lohi J, Hyytiäinen M,
Kilpinen S, Kallioniemi O, Ingvarsen S, Engelholm LH, Taipale
J, Alitalo K, Keski-Oja J, Lehti K. Fibroblast growth factor
Atlas Genet Cytogenet Oncol Haematol. 2012; 16(11)
808