IGF2-AS

Gene Summary


HPRD
Gene:IGF2-AS; IGF2 antisense RNA
Aliases: PEG8, IGF2AS, IGF2-AS1
Location:11p15.5
Summary:This gene expresses a paternally imprinted antisense transcript of the insulin-like growth factor 2 gene. The transcript is overexpressed in Wilms' tumor. This gene is predicted to be non-coding because the predicted protein is not conserved in any other species and the majority of transcripts would be candidates for non-sense mediated decay (NMD) if a protein were expressed. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2009]
Databases:OMIM, HGNC, Ensembl, GeneCard, Gene
Source:NCBIAccessed: 27 February, 2015

Cancer Overview

Research Indicators

Publications Per Year (1990-2015)
Graph generated 27 February 2015 using data from PubMed using criteria.

Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

  • Work Schedule Tolerance
  • Insulin-Like Growth Factor Binding Protein 3
  • Exons
  • snRNP Core Proteins
  • Signal Transduction
  • Neoplasm Proteins
  • RTPCR
  • Cell Cycle
  • Polymorphism
  • Gene Expression
  • Embryo, Mammalian
  • RNA, Untranslated
  • Messenger RNA
  • Genomic Imprinting
  • Wilms Tumour
  • Base Sequence
  • Wnt Signaling Pathway
  • Cancer Gene Expression Regulation
  • IGF2
  • Kidney Cancer
  • Biological Markers
  • Transcription Factors
  • Chromosome 11
  • Insulin-Secreting Cells
  • Proteins
  • Promoter Regions
  • DNA Methylation
  • Alleles
  • Hepatocellular Carcinoma
  • Mice, Transgenic
  • Tumor Markers
  • Long Noncoding RNA
  • Neoplastic Cell Transformation
  • Liver Cancer
  • Young Adult
  • Oligonucleotide Array Sequence Analysis
  • Tyrosine 3-Monooxygenase
  • IGF2 protein, mouse
  • p53 Protein
  • Gene Expression Regulation
Tag cloud generated 27 February, 2015 using data from PubMed, MeSH and CancerIndex

Specific Cancers (3)

Data table showing topics related to specific cancers and associated disorders. Scope includes mutations and abnormal protein expression.

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Latest Publications: IGF2-AS (cancer-related)

Cao Y, Lindström S, Schumacher F, et al.
Insulin-like growth factor pathway genetic polymorphisms, circulating IGF1 and IGFBP3, and prostate cancer survival.
J Natl Cancer Inst. 2014; 106(6):dju085 [PubMed] Article available free on PMC after 01/06/2015 Related Publications
BACKGROUND: The insulin-like growth factor (IGF) signaling pathway has been implicated in prostate cancer (PCa) initiation, but its role in progression remains unknown.
METHODS: Among 5887 PCa patients (704 PCa deaths) of European ancestry from seven cohorts in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium, we conducted Cox kernel machine pathway analysis to evaluate whether 530 tagging single nucleotide polymorphisms (SNPs) in 26 IGF pathway-related genes were collectively associated with PCa mortality. We also conducted SNP-specific analysis using stratified Cox models adjusting for multiple testing. In 2424 patients (313 PCa deaths), we evaluated the association of prediagnostic circulating IGF1 and IGFBP3 levels and PCa mortality. All statistical tests were two-sided.
RESULTS: The IGF signaling pathway was associated with PCa mortality (P = .03), and IGF2-AS and SSTR2 were the main contributors (both P = .04). In SNP-specific analysis, 36 SNPs were associated with PCa mortality with P trend less than .05, but only three SNPs in the IGF2-AS remained statistically significant after gene-based corrections. Two were in linkage disequilibrium (r 2 = 1 for rs1004446 and rs3741211), whereas the third, rs4366464, was independent (r 2 = 0.03). The hazard ratios (HRs) per each additional risk allele were 1.19 (95% confidence interval [CI] = 1.06 to 1.34; P trend = .003) for rs3741211 and 1.44 (95% CI = 1.20 to 1.73; P trend < .001) for rs4366464. rs4366464 remained statistically significant after correction for all SNPs (P trend.corr = .04). Prediagnostic IGF1 (HRhighest vs lowest quartile = 0.71; 95% CI = 0.48 to 1.04) and IGFBP3 (HR = 0.93; 95% CI = 0.65 to 1.34) levels were not associated with PCa mortality.
CONCLUSIONS: The IGF signaling pathway, primarily IGF2-AS and SSTR2 genes, may be important in PCa survival.

Jacobs DI, Hansen J, Fu A, et al.
Methylation alterations at imprinted genes detected among long-term shiftworkers.
Environ Mol Mutagen. 2013; 54(2):141-6 [PubMed] Related Publications
Exposure to light at night through shiftwork has been linked to alterations in DNA methylation and increased risk of cancer development. Using an Illumina Infinium Methylation Assay, we analyzed methylation levels of 397 CpG sites in the promoter regions of 56 normally imprinted genes to investigate whether shiftwork is associated with alteration of methylation patterns. Methylation was significantly higher at 20 CpG sites and significantly lower at 30 CpG sites (P < 0.05) in 10 female long-term shiftworkers as compared to 10 female age- and folate intake-matched day workers. The strongest evidence for altered methylation patterns in shiftworkers was observed for DLX5, IGF2AS, and TP73 based on the magnitude of methylation change and consistency in the direction of change across multiple CpG sites, and consistent results were observed using quantitative DNA methylation analysis. We conclude that long-term shiftwork may alter methylation patterns at imprinted genes, which may be an important mechanism by which shiftwork has carcinogenic potential and warrants further investigation.

Simon DP, Hammer GD
Adrenocortical stem and progenitor cells: implications for adrenocortical carcinoma.
Mol Cell Endocrinol. 2012; 351(1):2-11 [PubMed] Article available free on PMC after 01/06/2015 Related Publications
The continuous centripetal repopulation of the adrenal cortex is consistent with a population of cells endowed with the stem/progenitor cell properties of self-renewal and pluripotency. The adrenocortical capsule and underlying undifferentiated cortical cells are emerging as critical components of the stem/progenitor cell niche. Recent genetic analysis has identified various signaling pathways including Sonic Hedgehog (Shh) and Wnt as crucial mediators of adrenocortical lineage and organ homeostasis. Shh expression is restricted to the peripheral cortical cells that express a paucity of steroidogenic genes but give rise to the underlying differentiated cells of the cortex. Wnt/β-catenin signaling maintains the undifferentiated state and adrenal fate of adrenocortical stem/progenitor cells, in part through induction of its target genes Dax1 and inhibin-α, respectively. The pathogenesis of ACC, a rare yet highly aggressive cancer with an extremely poor prognosis, is slowly emerging from studies of the stem/progenitor cells of the adrenal cortex coupled with the genetics of familial syndromes in which ACC occurs. The frequent observation of constitutive activation of Wnt signaling due to loss-of-function mutations in the tumor suppressor gene APC or gain-of-function mutation in β-catenin in both adenomas and carcinomas, suggests perhaps that the Wnt pathway serves an early or initiating insult in the oncogenic process. Loss of p53 might be predicted to cooperate with additional genetic insults such as IGF2 as both are the most common genetic abnormalities in malignant versus benign adrenocortical neoplasms. It is unclear whether other factors such as Pod1 and Pref1, which are implicated in stem/progenitor cell biology in the adrenal and/or other organs, are also implicated in the etiology of adrenocortical carcinoma. The rarity and heterogeneous presentation of ACC makes it difficult to identify the cellular origin and the molecular progression to cancer. A more complete understanding of adrenocortical stem/progenitor cell biology will invariably aid in characterization of the molecular details of ACC tumorigenesis and may offer new options for therapeutic intervention.

Hoshida Y
Molecular signatures and prognosis of hepatocellular carcinoma.
Minerva Gastroenterol Dietol. 2011; 57(3):311-22 [PubMed] Related Publications
Prognostic prediction is a vital component in clinical management of hepatocellular carcinoma (HCC) patients. Rapidly evolving genomic assays serve as flexible sources to discover molecular signatures that sensitively and specifically predict clinical outcome of the patients. Studies have identified molecular signatures of HCC tumors that depict biological aggressiveness yielded through activation of specific genes and molecular pathways such as MYC, AKT, TGF-beta, and IGF2 as well as inactivation of TP53 pathway. Despite the promise for tumor-derived signatures' role in therapeutic target discovery, their value as prognostic marker seems to be limited especially in early-stage HCC, which has been increasing as a result of successful implementation HCC surveillance for patients with liver cirrhosis. In contrast, non-tumor, diseased liver tissues turn out to be a rich source of molecular information to capture propensity to hepatocarcinogenesis and metastasis through dyregulation of growth signaling and inflammatory/oxidative stress/immune response. In addition, the liver-derived signatures hold prognostic relevance irrespective of HCC stage, suggesting their role as prognostic markers. Furthermore, they may also be utilized for development of HCC chemoprevention therapy.

Chava S, Mohan V, Shetty PJ, et al.
Immunohistochemical evaluation of p53, FHIT, and IGF2 gene expression in esophageal cancer.
Dis Esophagus. 2012; 25(1):81-7 [PubMed] Related Publications
The aim of the study was to evaluate the expression of tumor suppressor genes p53, fragile histidine triad gene (FHIT), and an oncogene insulin-like growth factor 2 (IGF2) as prognostic markers in the etiology of esophageal cancer. Immunohistochemistry (IHC) was performed in 39 archival tissue samples of different esophageal pathologies for the three genes. Abnormal p53 expression was maximum in all the cases of squamous cell carcinoma, while IGF2 expression was enhanced in squamous cell carcinoma (81%), adenocarcinoma (100%), and dysplasia of squamous epithelium (75%) samples when compared with normals (50%). To our surprise, 75% of normal tissues did not show FHIT expression, which was also not seen in 40% of dysplasias of squamous epithelium, 33.3% of adenocarcinoma, and 41% of squamous cell carcinoma. To the best of our knowledge, this is the first study evaluating IGF2 by IHC, as well as, correlating it with the expression of the two tumor suppressor genes, p53 and FHIT, in esophageal tissue. p53 expression was threefold higher than normal in dysplasias of squamous epithelium and adenocarcinoma, while it was eightfold higher in squamous cell carcinoma. IGF2 expression was low in normal and dysplasia tissue but was increased 1.97-fold in both types of malignancy. FHIT and p53 expression were well correlated in squamous cell carcinoma, supporting the observation that FHIT regulates and stabilizes p53. Altered/lowered FHIT levels may be a result of exposure to various exogenous agents; however, this could not be assessed in the present study as it was carried out on archival samples. A larger prospective study is warranted to establish the role of exogenous factors in FHIT expression.

Meyer-Rochow GY, Jackson NE, Conaglen JV, et al.
MicroRNA profiling of benign and malignant pheochromocytomas identifies novel diagnostic and therapeutic targets.
Endocr Relat Cancer. 2010; 17(3):835-46 [PubMed] Related Publications
MicroRNAs (miRNAs) are small RNAs ( approximately 22 bp) that post-transcriptionally regulate protein expression and are found to be differentially expressed in a number of human cancers. There is increasing evidence to suggest that miRNAs could be useful in cancer diagnosis, prognosis, and therapy. We performed miRNA microarray expression profiling on a cohort of 12 benign and 12 malignant pheochromocytomas and identified a number of differentially expressed miRNAs. These results were validated in a separate cohort of ten benign and ten malignant samples using real-time quantitative RT-PCR; benign samples had a minimum follow-up of at least 2 years. It was found that IGF2 as well as its intronic miR-483-5p was over-expressed, while miR-15a and miR-16 were under-expressed in malignant tumours compared with benign tumours. These miRNAs were found to be diagnostic and prognostic markers for malignant pheochromocytoma. The functional role of miR-15a and miR-16 was investigated in vitro in the rat PC12 pheochromocytoma cell line, and these miRNAs were found to regulate cell proliferation via their effect on cyclin D1 and apoptosis. These data indicate that miRNAs play a pivotal role in the biology of malignant pheochromocytoma, and represent an important class of diagnostic and prognostic biomarkers and therapeutic targets warranting further investigation.

Mutskov V, Felsenfeld G
The human insulin gene is part of a large open chromatin domain specific for human islets.
Proc Natl Acad Sci U S A. 2009; 106(41):17419-24 [PubMed] Article available free on PMC after 01/06/2015 Related Publications
Knowledge of how insulin (INS) gene expression is regulated will lead to better understanding of normal and abnormal pancreatic beta cell function. We have mapped histone modifications over the INS region, coupled with an expression profile, in freshly isolated islets from multiple human donors. Unlike many other human genes, in which active modifications tend to be concentrated within 1 kb around the transcription start site, these marks are distributed over the entire coding region of INS as well. Moreover, a region of approximately 80 kb around the INS gene, which contains the {tyrosine hydroxylase (TH)-(INS)-insulin-like growth factor 2 antisense (IGF2AS)-insulin-like growth factor 2 (IGF2)} gene cluster, unusually is marked by almost uniformly elevated levels of histone acetylation and H3K4 dimethylation, extending both downstream into IGF2 and upstream beyond the TH gene. This is accompanied by islet specific coordinate expression with INS of the neighboring TH and IGF2 genes. The presence of islet specific intergenic transcripts suggests their possible function in the maintenance of this unusual large open chromatin domain.

Dejeux E, Olaso R, Dousset B, et al.
Hypermethylation of the IGF2 differentially methylated region 2 is a specific event in insulinomas leading to loss-of-imprinting and overexpression.
Endocr Relat Cancer. 2009; 16(3):939-52 [PubMed] Related Publications
Prediction of the evolution of endocrine pancreatic tumors remains difficult based on histological criteria alone. We have previously demonstrated that epigenetic changes are an early event in a mouse model developing insulinomas. Particularly, overexpression of the imprinted IGF2 was caused by the hypermethylation of CpGs in the differentially methylated region 2 (DMR2). Here, we investigated whether IGF2 hypermethylation is also observed in human insulinomas and whether this alteration is common to other human endocrine tumors of the pancreas and the digestive tract. We analyzed the methylation status of 40 CpGs located in the DMR0 and DMR2 of the IGF2 as well as in the H19 DMR by pyrosequencing in a cohort of 62 patients with pancreatic or small intestine endocrine tumors. Altered methylation patterns were observed in all tumor types for the different regions of IGF2, but not for H19. However, hypermethylation of the IGF2 DMR2 was specific for insulinomas and did not occur in any of the other types of tumors which were characterized by a loss of methylation in this region. Gain of methylation in the IGF2 DMR2 in insulinomas correlated with loss-of-imprinting and promoter 4 mediated overexpression of IGF2 at the RNA and protein level. Furthermore, a decreasing degree of methylation in the different regions of IGF2 correlated well with increasing degree of malignancy according to the WHO classification of pancreatic endocrine tumors (PETs), suggesting that methylation of IGF2 might be a useful biomarker for classification and staging of PETs.

Linhart HG, Lin H, Yamada Y, et al.
Dnmt3b promotes tumorigenesis in vivo by gene-specific de novo methylation and transcriptional silencing.
Genes Dev. 2007; 21(23):3110-22 [PubMed] Article available free on PMC after 01/06/2015 Related Publications
Increased methylation of CpG islands and silencing of affected target genes is frequently found in human cancer; however, in vivo the question of causality has only been addressed by loss-of-function studies. To directly evaluate the role and mechanism of de novo methylation in tumor development, we overexpressed the de novo DNA methyltransferases Dnmt3a1 and Dnmt3b1 in Apc Min/+ mice. We found that Dnmt3b1 enhanced the number of colon tumors in Apc Min/+ mice approximately twofold and increased the average size of colonic microadenomas, whereas Dnmt3a1 had no effect. The overexpression of Dnmt3b1 caused loss of imprinting and increased expression of Igf2 as well as methylation and transcriptional silencing of the tumor suppressor genes Sfrp2, Sfrp4, and Sfrp5. Importantly, we found that Dnmt3b1 but not Dnmt3a1 efficiently methylates the same set of genes in tumors and in nontumor tissues, demonstrating that de novo methyltransferases can initiate methylation and silencing of specific genes in phenotypically normal cells. This suggests that DNA methylation patterns in cancer are the result of specific targeting of at least some tumor suppressor genes rather than of random, stochastic methylation followed by clonal selection due to a proliferative advantage caused by tumor suppressor gene silencing.

Soroceanu L, Kharbanda S, Chen R, et al.
Identification of IGF2 signaling through phosphoinositide-3-kinase regulatory subunit 3 as a growth-promoting axis in glioblastoma.
Proc Natl Acad Sci U S A. 2007; 104(9):3466-71 [PubMed] Article available free on PMC after 01/06/2015 Related Publications
Amplification or overexpression of growth factor receptors is a frequent occurrence in malignant gliomas. Using both expression profiling and in situ hybridization, we identified insulin-like growth factor 2 (IGF2) as a marker for a subset of glioblastomas (GBMs) that lack amplification or overexpression of EGF receptor. Among 165 primary high-grade astrocytomas, 13% of grade IV tumors and 2% of grade III tumors expressed IGF2 mRNA levels >50-fold the sample population median. IGF2-overexpressing tumors frequently displayed PTEN loss, were highly proliferative, exhibited strong staining for phospho-Akt, and belonged to a subclass of GBMs characterized by poor survival. Using a serum-free culture system, we discovered that IGF2 can substitute for EGF to support the growth of GBM-derived neurospheres. The growth-promoting effects of IGF2 were mediated by the insulin-like growth factor receptor 1 and phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3), a regulatory subunit of phosphoinositide 3-kinase that shows genomic gains in some highly proliferative GBM cases. PIK3R3 knockdown inhibited IGF2-induced growth of GBM-derived neurospheres. The current results provide evidence that the IGF2-PIK3R3 signaling axis is involved in promoting the growth of a subclass of highly aggressive human GBMs that lack EGF receptor amplification. Our data underscore the importance of the phosphoinositide 3-kinase/Akt pathway for growth of high-grade gliomas and suggest that multiple molecular alterations that activate this signaling cascade may promote tumorigenesis. Further, these findings highlight the parallels between growth factors or receptors that are overexpressed in GBMs and those that support in vitro growth of tumor-derived stem-like cells.

Cui H
Loss of imprinting of IGF2 as an epigenetic marker for the risk of human cancer.
Dis Markers. 2007; 23(1-2):105-12 [PubMed] Article available free on PMC after 01/06/2015 Related Publications
IGF2 is the first gene discovered to be imprinted and expressed exclusively from the paternal allele in both human and mouse. IGF2 is also the first imprinted gene displaying loss of imprinting (LOI) or aberrant imprinting in human cancers. Evidently, LOI or reactivation of the maternal allele of IGF2 is associated with an increase of IGF2 expression that may subsequently play an important role in the onset of human cancers. The most important discovery was the association of LOI of IGF2 with the risk of developing human colorectal cancer. LOI occurs not only in colon cancer tissues, but also in matched normal tissues and peripheral blood cells. A pilot study indicated a significant relationship between LOI of IGF2 and family history as well as personal history of colorectal cancer, suggesting that LOI of IGF2 might be a valuable biomolecular marker of predicting an individual's risk for colon cancer. A recent epigenetic progenitor model suggested that human cancers might have a common basis that involves an epigenetic disruption of progenitor cells mediated by "tumor progenitor genes" and proposed that non-neoplastic but epigenetically disrupted progenitor cells might be an important target for cancer risk assessment and prevention.

Gallagher E, Mc Goldrick A, Chung WY, et al.
Gain of imprinting of SLC22A18 sense and antisense transcripts in human breast cancer.
Genomics. 2006; 88(1):12-7 [PubMed] Related Publications
The 11p15.5 region harbors three imprinted sense/antisense transcript pairs, SLC22A18/SLC22A18AS, IGF2/IGF2AS (PEG8), and KCNQ1/KCNQ1OT1 (LIT1). SLC22A18 (solute carrier family 22 (organic cation transporter) member 18) and its antisense transcript SLC22A18AS are paternally suppressed in fetal samples. In adult tissue, SLC22A18 displays polymorphic imprinting, but the imprinting status of SLC22A18AS remains elusive. SLC22AI8 DNA-PCR-RFLP analysis using NlaIII restriction digestion identified SLC22A18 heterozygotes within this breast tissue cohort (n = 89). Commercial sequencing identified informative SLC22A18AS samples. Random hexamer-primed cDNA synthesis, SLC22A18/SLC22A18AS-specific PCR, and imprinting evaluation by commercial sequencing demonstrated that SLC22A18AS displays a nonimprinted profile in reduction mastectomies (n = 6). However, SLC22A18 showed a gain of imprinting (GOI) in 1/4 of these normal cases. In the malignant cohort, GOI was also demonstrated in 18% for SLC22A18 and 14% for SLC22A18AS, occurring concomitantly in one case. This study reports the imprinting status of SLC22A18AS in adult tissue, and shows that GOI affects both the sense, and antisense transcripts at this locus in human breast tissue.

Vu TH, Chuyen NV, Li T, Hoffman AR
Loss of imprinting of IGF2 sense and antisense transcripts in Wilms' tumor.
Cancer Res. 2003; 63(8):1900-5 [PubMed] Related Publications
Human insulin-like growth factor II gene (IGF2) is overexpressed, and its imprinting is disrupted in many tumors, including Wilms' tumor. A transcript that is antisense to IGF2, IGF2-antisense (IGF2-AS), is transcribed from within IGF2 in a reverse orientation. This transcript is also maternally imprinted and overexpressed in Wilms' tumor. IGF2-AS was detected as a 2.2 kb mRNA in Hep 3B cells by Northern blotting, and it encodes a putative 168 amino acid peptide. An alternative splicing mRNA observed predominantly in adult liver encodes an additional putative 199 amino acid peptide. We have examined the expression of IGF2 and IGF2-AS in normal tissue, breast and ovarian tumors, and 25 informative, well-characterized Wilms' tumors and determined the relationship between IGF2 and IGF2-AS imprinting. IGF2-AS was expressed at levels comparable with IGF2 sense expression derived from promoters P1 and P2 in normal tissue and in breast, ovarian, and Wilms' tumor tissues. In Wilms' tumors that demonstrate maintenance of imprinting of IGF2, IGF2-AS was imprinted. In contrast, in tumors which demonstrate LOI of IGF2, only two of six tumors showed loss of imprinting of IGF2-AS, whereas four of six tumors demonstrated maintenance of imprinting for IGF2-AS. The discrepancy between IGF2 and IGF2-AS loss of imprinting in some tumors demonstrates the control complexity of the imprinting status of the various transcripts derived from the IGF2 gene.

Nishihara S, Hayashida T, Mitsuya K, et al.
Multipoint imprinting analysis in sporadic colorectal cancers with and without microsatellite instability.
Int J Oncol. 2000; 17(2):317-22 [PubMed] Related Publications
Disrupted imprinting is implicated in certain tumorigenesis. Since aberrant methylation has been described for a majority of microsatellite instability (MSI)-positive sporadic colorectal cancers, we have investigated alteration to the imprinting in 55 sporadic colorectal cancers with or without MSI. Loss of imprinting (LOI) of IGF2 and PEG1/MEST was observed in 42% and 35% of informative cancers, respectively. H19 expression was not detected in 24% of informative cancers. SNRPN and NDN retained monoallelic expression in all the cancers examined. These findings indicate no simultaneous disruption of the imprinted genes. LOI of IGF2 and PEG1/MEST was also observed in colorectal mucosa from almost all the patients with LOI in tumor tissue. Moreover, MSI-positive colorectal cancers exhibit LOI of IGF2 with a high frequency compared to MSI-negative cancers (P=0.013). These observations, consistent with a previous report, establish an association between LOI of IGF2 and MSI in colorectal cancers and provide insight into susceptibility of tumor development.

Okutsu T, Kuroiwa Y, Kagitani F, et al.
Expression and imprinting status of human PEG8/IGF2AS, a paternally expressed antisense transcript from the IGF2 locus, in Wilms' tumors.
J Biochem. 2000; 127(3):475-83 [PubMed] Related Publications
A large imprinted gene cluster in human chromosome 11p15.5 has been implicated in Beckwith-Wiedemann syndrome and Wilms' tumor. We have identified a paternally expressed imprinted gene, PEG8/IGF2AS, in this locus. It is transcribed in the opposite direction to the IGF2 transcripts and some genomic regions are shared with the IGF2 gene, as in the case of the mouse imprinted Igf2as gene reported previously by T. Moore et al. As to the relationship between these genomic regions, the human and mouse genes are very similar but there is no homology in their middle parts. Interestingly, PEG8/IGF2AS and IGF2 were found to be overexpressed in Wilms' tumor samples, at levels over ten and a hundred times higher than that in normal kidney tissues neighboring the tumors, respectively. These findings indicate that PEG8/IGF2AS is a good marker of Wilms' tumor and also suggest the possibility of PEG8/IGF2AS being one of the candidate Wilms' tumor genes.

Li X, Nong Z, Ekström C, et al.
Disrupted IGF2 promoter control by silencing of promoter P1 in human hepatocellular carcinoma.
Cancer Res. 1997; 57(10):2048-54 [PubMed] Related Publications
Previous investigations have supported or indicated a stimulatory role of the insulin-like growth factor II gene (IGF2) in hepatocarcinogenesis. We have studied the transcript levels, promoter usage, and imprinting status of the ICF2 gene and its relationship to H19 in human hepatocellular carcinomas (HCCs) and liver tumor cell lines. The activity of the IGF2 promoter P1 was lost in about 70% of the cases (18 of 25). This is the most prominent abnormality regarding the IGF2 regulation in this study. Total IGF2 as well as promoter P3 transcription were up-regulated in a small group of the tumors. Twenty genetically informative cases were obtained from 26 cases, thus excluding the probability of loss of heterozygosity of the IGF2 gene. Among these, nine showed abnormal monoallelic expression of IGF2. One HCC and one HCC cell line proved loss of functional imprinting of IGF2. H19 and IGF2 were regulated in parallel, and expression levels were variable. Taken together, the disruption of the IGF2 promoter regulation, particularly the loss of P1 activity, is a common feature of human HCCs. The loss of P1 activity explains the frequent loss of biallelic IGF2 expression and may potentially be used as a diagnostic or monitoring marker for human HCC.

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Cite this page: Cotterill SJ. IGF2-AS, Cancer Genetics Web: http://www.cancer-genetics.org/IGF2-AS.htm Accessed:

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