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Supplementary Table. Differentially expressed genes in intravenous leiomyomatosis compared to uterine leiomyoma with t(12;14) (p<0.05)
Gene
Chromosome
band
Nucleotide
(GRCh37/hg19)
p-value
11q23.3
118,230,296118,269,926
0.003
2. CTTN*
11q13
70,244,51070,282,690
0.004
3. TNPO1
5q13.2
72,112,13972,212,560
0.009
4. GPX3*
5q33.1
150,399,999150,408,554
0.009
5. MDM2*
12q14
69,201,95669,239,214
0.009
6. CFH*
1q31.3
196,621,008196,716,634
0.011
7. EFEMP1*
2p16.1
56,093,09756,151,298
0.015
1. UBE4A*
Function and involvement in cancer
-Ubiquitination Factor E4A: involved in multiubiquitin chain assembly and critical
role in chromosome condensation and separation (1)
-Involved in protecting the cell from environmental stress and that inactivation of
UBE4A contributes to malignancy in neuroblastoma (2)
-Cortactin: a key regulator of the actin cytoskeleton, role in many actin-based
cellular processes, including cell migration and invasion, tumor cell metastasis,
and endocytosis (3)
-Overexpression is associated with poor prognosis, invasion, and metastasis
in multiple cancer types (4-6)
-Transportin 1: interaction with nuclear localization signals to target nuclear
proteins to the nucleus (7)
-Glutathione Peroxidase 3: detoxification of hydrogen peroxide (8)
-Hypermethylation and underexpression occur commonly in prostate, gastric,
cervical, thyroid, and colon cancers (9-12), and therefore presumed to be a tumor
suppressor gene
-Loss of GPX3 expression closely associated with clinical pathological behavior
and poor prognosis of gallbladder cancer (13)
-MDM2
proto-oncogene,
E3
ubiquitin
protein
ligase:
inducing cell cycle arrest or apoptosis in response to cellular stress, targeting the
p53 protein for proteasomal degradation (14)
-Oncogenic activity in many cancer types by inhibiting the p53 tumor
suppressor (15)
-Complement Factor H: role in the regulation of complement activation (16)
-Increased CpG site methylation and decreased mRNA expression of CFH
associated with recurrence of hepatocellular carcinoma (17)
-Downregulated in colorectal cancer in comparison to both colorectal adenoma
and normal tissue, downregulated in colorectal adenoma in comparison to normal
tissue, a marker for adenoma to adenocarcinoma progression (18)
-EGF Containing Fibulin-Like Extracellular Matrix Protein 1: encoding a member
of the fibulin family of extracellular matrix glycoproteins (19)
-Decreased expression in hepatocellular (20) and gastric cancer (21) in
comparison to normal tissue, and in prostate cancer in comparison to benign
prostatic hyperplasia (22)
-Hypermethylation and decreased expression of EFEMP1 promoter correlated
with poor prognosis (invasion and metastasis) in multiple cancer types (20-24)
-Overexpression associated with poor clinicopathologic features and promotes
angiogenesis in ovarian carcinoma (25)
-Casein Kinase 1, Alpha 1: regulation of Smo cell surface accumulation and
activity in response to hedgehog (26)
-Downregulation causes a senescence-inflammatory switch from cancerinhibitory to cancer-promoting mechanism (27)
- Functions as a tumor suppressor when p53 is inactivated (28)
-Insulin-Like Growth Factor 1 Receptor: insulin-like growth factors bind to IGF1R
and activate downstream signaling pathways, including PI3K-AKT/PKB signaling
which is associated with cancer, and therefore IGF1R is important for tumor
transformation and survival of malignant cells (29-31)
-Overexpressed in multiple tumors including melanomas, cancers of the colon,
pancreas prostate and kidney
-Overexpression of IGFR1 correlates with postoperative recurrence of lung
adenocarcinoma (32)
-Interferon Induced Transmembrane Protein: a member of the interferon inducible
transmembrane protein family (33)
-Mediation of the antiproliferative effect of IFN-Ɣ and cell proliferation arrest in
a p53-dependent manner (34)
-Downregulated expression of IFITM1 in low-grade diffuse astrocytomas and
breast cancer (35, 36)
-Overexpression promotes metastasis and enhances the metastatic phenotype
in ovarian cancer (37)
-Overexpression is a marker of endometrial stromal differentiation across the
spectrum from proliferative endometrium to metastatic stromal sarcoma (38)
-Ornithine Aminotransferase: mitochondrial enzyme converting arginine and
ornithine
-Overexpressed in androgen-independent prostate cancer in comparison to
androgen-dependent prostate cancer (Androgen-dependent prostate cancer
may progress into androgen-independent with poor prognosis after androgen
ablation therapy) (39, 40)
-Integrin, Alpha 7: integral membrane protein (41)
-Tumor suppressor gene, critical for suppressing the growth of malignant
tumors including prostate cancer, liver cancer, glioblastoma multiforme, and
leiomyosarcoma (42)
5q32
148,871,760148,931,007
0.018
9. IGF1R*
15q26.3
99,192,20099,507,759
0.021
10. IFITM1*
11p15.5
313,506315,272
0.022
11. OAT*
10q26.13
126,085,872126,107,545
0.023
12. ITGA7*
12q13.2
56,078,35256,109,827
0.028
13. HBA1
16p13.3
226,679227,521
0.029
-Hemoglobin, alpha 1 (43)
14. TIA1
2p13.3
70,436,57670,475,792
0.03
T-Cell-Restricted Intracellular Antigen-1:
pre-RNA alternative splicing and
regulation of mRNA translation, cytotoxic granule-associated protein expressed in
natural killer cells and cytotoxic T lymphocytes (44)
8. CSNK1A1*
-Collagen, Type III, Alpha: encoding pro-alpha1 chains of Type III fibrillar collagen
-Increased expression associated with tumor progression in muscle-invasive
and metastatic bladder transitional cell carcinoma in comparison to noninvasive stage bladder cancer or normal bladder tissue (45) (also see
COL5A1 and CDKN2B)
-Transcription Factor 12: DNA binding protein (46)
-Overexpressed in metastatic colorectal cancer (47), and overexpression
associated with enhancement of colorectal cancer cell migration and invasion
(48)
15. COL3A1*#
2q32.2
189,839,046189,877,472
0.03
16. TCF12*
15q21.3
57,210,82157,591,479
0.031
17. RPS24
10q22.3
79,793,51879,816,571
0.032
-Ribosomal Protein S24: processing of pre-rRNA and maturation of 40S ribosomal
subunits (49)
18. ITGB3BP
1p31.3
63,906,44164,059,392
0.034
-Integrin Beta 3 Binding Protein: transcriptional coregulator enhancing activity of
members of the nuclear receptor families (50)
19. IL1R1
2q11.2
102,681,004102,796,334
0.034
20. XIST*
Xq13.2
73,040,48673,072,588
0.035
21. TAF1C
16q24.1
84,211,45884,220,669
0.035
22. ZNF84
12q24.33
133,613,878133,639,885
0.036
Zinc Finger Protein 84: DNA binding and zinc ion binding, may be involved in
transcriptional regulation (57)
23. FXR1*
3q26.33
180,585,929180,700,541
0.036
-Fragile X Mental Retardation, Autosomal Homolog 1: development of muscle
tissue, intracellular transport and local translation of certain mRNAs (58)
-Overexpressed in lung cancer (59)
-Candidate tumor suppressor gene in colon cancer (60)
24. NACA
12q13.3
57,106,21157,125,412
0.038
25. CDKN2B*#
9p21.3
22,002,90222,009,362
0.04
-Interleukin 1 Receptor, Type I: involved in many cytokine induced immune and
inflammatory responses (51)
-X Inactive Specific Transcript (Non-Protein Coding): initiation and spread of Xinactivation (52, 53)
-Conditional knock-out of Xist in the hematopoietic compartment leads to an
aggressive form of hematologic cancer in female mice (54)
-Reactivation of inactive X has been reported in multiple cancer types (55)
TATA Box-Binding Protein-Associated Factor RNA Polymerase I Subunit C:
assembly preinitiation complex in RNA polymerase I associated transcription (56)
Nascent Polypeptide Associated Complex Alpha Subunit:
prevents
mistranslocation of nascent proteins to the endoplasmic reticulum (61)
-Cyclin-Dependent Kinase Inhibitor 2B, also known as Multiple Tumor
Suppressor 2: cell growth regulator that controls cell cycle G1 progression and
role in the TGF beta induced growth inhibition (62)
-Loss of CDKN2B is detected in malignant squamous head and neck cancer, in
comparison to non-malignant tissue (63)
-Loss of CDKN2A/B significant in mutant K-ras lung tumorigenesis by fostering
cellular proliferation, cancer cell differentiation and metastatic behavior (64)
-Muscle invasive urothelial tumors have deletion of CDKN2B (45, 65) (also
see COL3A1 and COL5A1)
6q13
74,225,47374,233,520
0.04
27. HSP90AA1*
14q32.31
102,547,075102,606,086
0.041
28. IFITM2*
11p15.5
307,631315,272
0.043
29. SORL1*
11q24.1
121,322,912121,504,471
0.044
30. C5orf13*
5q22.1
110,998,318111,333,161
0.046
31. HBB*
11p15.4
5,246,6945,250,625
0.046
26. EEF1A1*
-Eukaryotic Translation Elongation Factor 1 Alpha 1: enzymatic delivery of
aminoacyl tRNAs to the ribosome (66)
-Overexpression of EF1A protein related to cell proliferation and cancer
development in many tumors including head and neck, breast, prostate, colon,
lung, stomach, leukemia and hepatocarcinoma
-Inhibition of proliferation, invasion, and migration of prostate cancer cells by
downregulation of EF1A expression (67)
-Truncated form of EEF1A1 known as prostate tumor inducing gene 1 shown to
be expressed in prostate carcinoma patient-derived blood samples and proposed
to be a sensitive biomarker for prostate cancer (68), also shown to be expressed
in prostate cancer tissues but not in benign prostatic hyperplasia or normal
prostate (69)
-High EEF1A1 protein associated with metastatic progression of prostate
cancer (70)
-Heat Shock Protein 90kDa Alpha (Cytosolic), Class A Member 1: chaperone
helping protein folding and quality control of client proteins, role in some tumor cell
types by stabilizing mutated oncogenic proteins (71) (72)
-Overexpressed both in metastatic gastric cancer compared with primary
gastric cancer, and in primary gastric cancer compared with normal mucosa
(73)
-Interferon Induced Transmembrane Protein 2: inducible by type I and type II
interferons
-Overexpressed in colorectal tumors (74)
-Sortilin-related Receptor, L(DLR class) A Repeats Containing:
Role in
endocytosis and sorting (75)
-Downregulated in high grade astrocytoma in comparison to low grade
astrocytoma (76)
-Overexpressed in acute leukemia (77)
-Also named as Neuronal Regeneration Related Protein or P311: promotes
axonal regeneration, involved in cell migration, induces differentiation of
fibroblasts into myofibroblasts and myofibroblast ameboid migration (78)
-Identified as glioblastoma invasion gene (increased expression at the
invasive edge of the tumor) (79), overexpression also induces glioma motility
and invasion (80)
-Hemoglobin, beta (81)
-Decreased expression in anaplastic thyroid cancer and inhibition of cell
growth by recovery of its expression (82)
-Expression is associated with more aggressive metastatic phenotype in
breast cancer cells disseminated to bone (83)
32. CMKLR1*
12q23.3
108,681,821108,733,118
0.047
33. COL5A1*#
9q34.3
137,533,620137,736,689
0.047
-Chemokine-Like Receptor 1: involved in intracellular signaling and act as a
receptor to chemerin (84)
-Inhibition of in vivo melanoma growth with chemerin requires expression of
CMKLR1 (85)
-Higher expression associated with progression of normal esophageal
mucosa to mild and moderate squamous dysplasia (86)
-Collagen, Type V, Alpha 1: encoding an alpha chain for one of the Type V fibrillar
collagen (87)
-Increased expression associated with tumor progression and muscle-invasive
and metastatic bladder transition cell carcinoma in comparison to noninvasive stage bladder cancer or normal bladder tissue (45) (also see
COL3A1 and CDKN2B)
-Increased expression is associated with poor survival in high-grade serous
ovarian cancer (88)
Red: Up-regulated genes Blue: Down-regulated genes
*Up or down regulation is associated with cancer or a severe phenotype including poor prognosis, progression, invasion, migration, and metastasis.
#
Increased expression of fibrillar collagens COL5A1 and COL3A1, and Deletion of CDKN2B has been shown to support progression of muscleinvasive bladder tumors through invasion and metastasis (45, 65).
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