Table 1.

3q26 Gene Network

Gene	Product and function	Role in cancer	Impact of overexpression/amplification	References
ACTL6A	Actin-Like 6A, (aka: BAF53, ARP4) is an actin binding protein that plays a role in ATP-dependent chromatin remodeling.	ACTL6A binds the SWI/SNF complex in progenitor cells to prevent expression of differentiation genes. ACTL6A has a potential role in cancer stem cell function.	None described.	(Bao et al., 2013)
DCUN1D1	Defective in cullin neddylation 1, domain-containing 1 (aka: Squamous cell carcinoma-related oncogene, SCRO) regulates neddylation of E3 complex and regulates complex assembly and activation.	DCUN1D1 is required for survival of 3q amplified cancer cell lines. DCUN1D1 binds and activates GLI1 promoter in SCC cells.	DCUN1D1 is overexpressed in tumors with 3q copy number gains. DCUN1D1 amplification and expression correlates with poor clinical outcome in SCC. DCUN1D1 is predicted to be a driver mutation in 3q26-29 amplified LSCC.	(Kim et al., 2008) (Sarkaria et al., 2006) (Wang, Qian, 2013a)
DNAJC19	DNAJ (Hsp40) Homolog, Subfamily C, Member 19-(aka: Mitochondrial Import Inner Membrane Translocase Subunit TIM14) is a member of the co-chaperone system that imports proteins to the inner mitochondrial membrane. Mutations in this gene are associated with cardiomyopathy.	DNAJC19 mRNA expression is reduced in breast cancer ALDH1+ cancer stem cells. DNAJC19 mRNA expression is elevated in ovarian tumor compared to normal ovarian epithelium.	RNAi-mediated knockdown (KD) of DNAJC19 in 3q26 amplified ESCC and LSCC cell lines has no effect on anchorage-independent growth.	(Charafe-Jauffret et al., 2009) (Chen et al., 2012b) (Bass, Watanabe, 2009)
ECT2	Epithelial cell transforming 2 is a guanine nucleotide exchange factor for the Rho family of GTPases.	ECT2 is highly expressed in many tumor types, and required for lung cancer and glioma cell growth.	ECT2 expression is associated with poor prognosis in HNSCC, glioblastoma and ESCC.	(Hirata, Yamabuki, 2009) (Salhia, Tran, 2008) (Sano, Genkai, 2006) (Justilien and Fields, 2009) (Fields and Justilien, 2010)
EIF5A2	Eukaryotic translation initiation factor 5A2 binds mRNA and functions in the initiation and elongation processes of protein synthesis.	EIF5A2 KD in ESCC cell lines increases sensitivity to chemotherapy. EIF5A2 KD in gastric cancer cells suppresses growth, migration and invasion.	EIF5A2 expression predicts poor prognosis in NSCLC, ovarian, gastric, liver and esophageal cancers.	(Mathews and Hershey, 2015) (Yang et al., 2015) (Meng et al., 2015)
GNB4	Guanine Nucleotide Binding Protein (G Protein), Beta Polypeptide 4 encodes a heterotrimeric G-protein beta subunit. Functions downstream of G-protein coupled receptors (GPCR) and mutation in this gene impacts GPCR signaling in some inherited neuropathies.	High expression of GNB4 predicts survival in tamoxifen-treated recurrent breast cancer patients. Intronic haplotypes of GNB4 predict survival of colorectal and bladder cancer patients.	None described.	(Soong et al., 2013) (Umar et al., 2009) (Riemann et al., 2009) (Riemann et al., 2008)
GOLIM4	Golgi integral membrane protein 4, (aka: Golgi phosphoprotein of 130 kDa, GPP130) is a member of the Golgi complex that sorts and modifies proteins exported from the endosome to the Golgi. GOLIM4 cycles between endosome and Golgi in a pH-dependent manner.	None described.	None described.
MRPL47	Mitochondrial Ribosomal Protein L47 is a mitochondrial ribosomal protein member of the large 39S subunit.	None described.	None described.
NDUFB5	NADH Dehydrogenase (Ubiquinone) 1 Beta sub-complex 5 is an oxidative phosphorylation member of mitochondrial complex 1. NDUFB5 transfers electrons from NADH to ubiquinone.	NDUFB5 expression is decreased in ErbB2/Neu-initiated mammary tumor cells.	None described.	Klimcakova E, Cancer Res 2012
NAALADL2	N-acetylated alpha-linked acidic dipeptidase-like 2 is a member of the glutamate carboxypeptidase II family.	NAALADL2 was identified as a novel loci associated with prostate cancer aggressiveness. NAALADL2 expression predicts poor survival after prostatectomy. NAALADL2 positively regulates migration, invasion and anchorage-independent growth in a prostate cancer cell line.	None described.	(Berndt et al., 2015) (Whitaker et al., 2014)
PDCD10	Programmed cell death 10 (aka: cerebral cavernous malformation 3; CCM3) is associated with apoptosis; functions in vascular stability.	PDCD10 is upregulated in prostate cancer. PDCD10 is proposed to function in the PI3K pathway via interaction with PtdIns(3,4,5)P3.	None described.	(Hilder et al., 2007) (You et al., 2013) (Zhang et al., 2014)
PIK3CA	Phosphatidy-linositol-4,5-Bisphosphate 3-Kinase, Catalytic Subunit Alpha encodes the catalytic subunit of class 1 phosphatidyl-inositol 3-kinase (PI3K); phosphorylates PtdIns4P and PtdIns (4,5)P2.	PI3K signaling is elevated in cancers with mutant and amplified PIK3CA. PI3K is activated by oncogenic K-ras or receptor tyrosine kinases in many cancers to promote proliferative signaling, cell motility, invasion and protein synthesis.	PIK3CA copy number gains correlate with increased expression in 3q-amplified tumors (endometrial, gastric, LSCC, ovarian). PIK3CA mutation or amplification predicts cervical cancer response to cisplatin. PIK3CA copy number predicts poor survival in HNSCC and gastric cancer.	(Salvesen, Carter, 2009) (Byun, Cho, 2003) (Yamamoto, Shigematsu, 2008) (Wang et al., 2015a) (Suda et al., 2012) (Shi et al., 2012) (Shayesteh, Lu, 1999)
PLD1	Phospholipase D1 is a phosphatidylcholine (PC)-specific phospholipase that catalyzes hydrolysis of phosphatidylcholine to form phosphatidic acid and choline.	PLD1 functions in a positive feedback loop to promote Wnt/beta-catenin signaling in cancer cells. PLD1 inhibition promotes autophagic flux and sensitizes cancer to inhibition of autophagy. PLD1 in microenvironment promotes tumor metastasis and tumor vascularization.	None described.	(Kang et al., 2010) (Dall’Armi et al., 2010) (Chen et al., 2012a)
PRKCI	Protein kinase C, iota (PKCι) is a serine/threonine protein kinase.	PKCι regulates cancer cell proliferation and transformed phenotype in lung, pancreatic, ovarian cancers and glioma. PKCι is required for cancer stem cell phenotype in ovarian and LSCC.	PRKCI amplification is associated with elevated expression and poor prognosis in LSCC, HNSCC and ESCC, as well as other 3q amplified tumors.	(Regala et al., 2005a) (Regala, Weems, 2005b) (Scotti, Bamlet, 2010) (Justilien, Walsh, 2014) (Desai et al., 2011) (Wang, Hill, 2013b) (Murray, Kalari, 2011)
SEC62	SEC62 Homolog (aka: Translocation protein 1, TLOC1) regulates protein translation and processing in the endoplasmic reticulum (ER) and transport across the ER membrane.	SEC62 is a prognostic marker in NSCLC. SEC62 mediates resistance to ER stress in prostate cancer and NSCLC cell lines.	SEC62 KD reduces transformed growth of 3q26 amplified cancer cell lines. High SEC62 mRNA and protein expression correlates with 3q26 copy number gains. Elevated expression of SEC62 correlates with lymph node metastasis and poor differentiation in LSCC.	(Hagerstrand, Tong, 2013) (Linxweiler et al., 2012) (Linxweiler et al., 2013) (Greiner et al., 2011) (Jung et al., 2006)
SKIL	SKI-like proto-oncogene (aka: SNO) is a negative regulator of TGFβ-Smad signaling that also stabilizes p53 and induces senescence.	Overexpression of SKIL may contribute to tumor cell resistance to the growth-inhibitory effects of TGFβ. SKIL promotes invasion via up-regulation of SLUG, and induces xenograft tumor growth.	SKIL expression correlates with copy number in ESSC cell lines. SKIL expression correlates with poor prognosis in ESCC.	(Imoto, Pimkhaokham, 2001) (Hagerstrand, Tong, 2013) (Akagi et al., 2008)
SMC4	Structural maintenance of chromosomes 4 is an ATPase involved in chromosome condensation in early mitosis. SMC4 regulates chromosomal segregation and assembly.	SMC4 regulates JAK/STAT signaling. SMC4 KD in HCC reduces in vitro and in vivo growth.	Elevated expression of SMC4 in HCC is associated with progression.	(Zhou et al., 2012) (Zhou et al., 2014)
SOX2	SRY (Sex Determining Region Y)-Box 2 is a transcription factor that regulates gene expression in development and stem cell maintenance.	SOX2 is required for the cancer stem cell phenotype in LSCC and HNSCC.	SOX2 expression in HNSCC predicts poor survival.	(Justilien, Walsh, 2014) (Lee, Oh, 2014) (Dong, Liu, 2014)
TBL1XR1	Transducin-beta-like 1 X-linked receptor 1 is a member of nuclear receptor corepressor that represses or activates gene expression, depending on the regulatory complexes involved.	TBL1XR1 regulates β-catenin-mediated gene expression and breast cancer cell proliferation. TBL1XR1 activates NF-κB and cisplatin resistance in nasopharyngeal cancer. TBL1XR1 promotes EMT in cervical cancer and promotes VEGF-C expression and lymph-angiogenesis and lymph node metastasis.	TBL1XR1 is highly expressed and prognostic for poor survival in breast, cervical, nasopharyngeal and ESCC cancers.	(Li et al., 2014) (Li and Wang, 2008) (Chen et al., 2014b) (Liu et al., 2015)
TNFSF10	Tumor necrosis factor ligand superfamily member 10 (aka: TNF-related apoptosis-inducing ligand: TRAIL) is a cytokine belonging to the TNF ligand family that binds pro-apoptotic death receptors to transduce an apoptotic signal.	Loss of TNFSF10 expression in cervical cancer is associated with worse differentiation.	TNFSF10 expression in cervical cancer cell lines is down-regulated despite gene amplification.	(Yao et al., 2015) (Vazquez-Mena et al., 2012)
USP13	Ubiquitin specific peptidase 13 (aka: isopeptidase T-3) is a deubiquitinase enzyme implicated in tumor promotion and suppression by regulating stability of tumor suppressors and autophagy mediators.	USP13 de-ubiquitinates and stabilizes MITF to promote melanoma growth and tumorigenesis. USP13 stabilizes PTEN in breast cancer to suppress tumorigenesis and stabilizes autophagy regulators beclin1 and USP10.	None described.	(Zhao et al., 2011) (Zhang et al., 2013) (Liu et al., 2011a)