Aberrant imprinting of the insulin-like growth factor II receptor gene in Wilms' tumor

Xu, Y.; Grundy, Paul E.; Polychronakos, Constantin

doi:10.1038/sj.onc.1200926

Cited by 68 publications

(29 citation statements)

References 25 publications

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“…The M6p/Igf2r gene is imprinted in both mice (Barlow et al, 1991;Wang et al, 1994) and rats (Mills et al, 1998), whereas imprinting of the M6P/IGF2R is a polymorphic trait in humans with most adults expressing both alleles (Falls et al, 1999;. Thus, imprinting of the M6P/IGF2R could result in allelic inactivation, a postulate supported by the discovery that 50% of patients with Wilms' tumor are imprinted at this locus (Xu et al, 1997). Unfortunately, it was not possible to determine if M6P/IGF2R was imprinted in these lung tumors because RNA could not be isolated from the formalin ®xed, para n embedded tissues.…”

Section: Resultsmentioning

confidence: 99%

M6P/IGF2R is mutated in squamous cell carcinoma of the lung

et al. 2000

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Section: Resultsmentioning

confidence: 99%

M6P/IGF2R is mutated in squamous cell carcinoma of the lung

et al. 2000

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“…In humans, IGF2R imprinting is polymorphic, and monoallelic expression occurs in the preterm post-implantation embryo, but only in about 50% of individuals (38). Recently, Xu et al (39) showed that abnormal fetal imprinting of the IGF2R, with marked repression of the paternal allele, occurs with a frequency of 50% in Wilms' tumors. This tumor model has mechanisms of pathogenesis in common with adrenocortical tumors.…”

Section: Discussionmentioning

confidence: 99%

Loss of heterozygosity at the mannose 6-phosphate/insulin-like growth factor 2 receptor locus: a frequent but late event in adrenocortical tumorigenesis

Leboulleux

Gaston

Boulle

et al. 2001

European Journal of Endocrinology

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Objective: Recent studies have pointed to the role of the IGF system in adrenocortical tumorigenesis. The IGF-II gene is overexpressed in malignant adrenocortical tumors and its proliferative effects are mediated by the type-1 IGF receptor (IGF1R). The mannose 6-phosphate/IGF2 receptor (M6P/IGF2R) plays a key role in regulating cell growth, by ensuring the clearance and inactivation of IGF-II and facilitating activation of the growth inhibitor, transforming growth factor b (TGFb1). The M6P/ IGF2R has been implicated as a tumor suppressor gene in various human tumors. Methods: The purpose of this study was to determine if the M6P/IGF2R is involved in adrenal tumorigenesis. Two polymorphisms in the 3 H untranslated region of M6P/IGF2R were used to screen a large series of 76 sporadic adrenocortical tumors for loss of heterozygosity (LOH) by PCR amplification of DNA. Tumors were classified into three groups based on pathological features: benign tumors n 25Y suspect tumors n 22 and malignant tumors n 29X Results: LOH at the M6P/IGF2R locus was detected in 15 of 57 (26%) informative tumors and was more frequent in malignant tumors (58%) than in benign and suspect tumors (9 and 13% respectively). Conclusion: These findings provide evidence that LOH at the M6P/IGF2R locus is a frequent event in adrenocortical tumors and support the hypothesis that it may function as a tumor suppressor gene in adrenocortical tumorigenesis.

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“…[29][30][31] The expression of human and mouse IGF2R differs: in mice, Igf2r imprinted expression is observed in all fetal and adult tissues; in humans, IGF2R imprinted expression has not been found in adult tissues, but has been found in fetal tissues and Wilms' tumours, in a proportion of samples tested. 32 There is also a difference in the DMRs between these two species: DMR1, in the promoter of the Igf2r gene, occurs only in mice; DMR2 occurs in both species and is located in intron 2, methylated on the maternal allele. In mice the DMR2 acts as a promoter for Air, a non-coding RNA, which is antisense to Igf2r.…”

Section: Discussionmentioning

confidence: 99%

Methylation analysis of 79 patients with growth restriction reveals novel patterns of methylation change at imprinted loci

et al. 2010

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International audienceThis study was an investigation of 79 patients referred to the Wessex Regional Genetics Laboratory with suspected Russell-Silver Syndrome or unexplained short stature/intra uterine growth restriction, warranting genetic investigation. Methylation status was analysed at target sequences within eleven imprinted loci (PLAGL1, IGF2R, PEG10, MEST1, GRB10, KCNQ1OT1, H19, IGF2P0, DLK1, PEG3, NESPAS). 37% (29/79) of samples were demonstrated to have a methylation abnormality. The commonest finding was a loss of methylation at H19 (23/29), as previously reported in Russell-Silver Syndrome. In addition, four of these patients had methylation anomalies at other loci, of whom two show hypomethylation of multiple imprinted loci, and two showed a complete gain of methylation at IGF2R. This latter finding was also present in five further patients who did not have demonstrable changes at H19. In total, 7/79 patients showed a gain of methylation at IGF2R and this was significantly different from a normal control population of 267 individuals (p=0.002). This study demonstrates the importance of widening the epigenetic investigation to include multiple imprinted loci and highlights potential involvement of the IGF2R locus in growth restriction

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Aberrant imprinting of the insulin-like growth factor II receptor gene in Wilms' tumor

Cited by 68 publications

References 25 publications

M6P/IGF2R is mutated in squamous cell carcinoma of the lung

M6P/IGF2R is mutated in squamous cell carcinoma of the lung

Loss of heterozygosity at the mannose 6-phosphate/insulin-like growth factor 2 receptor locus: a frequent but late event in adrenocortical tumorigenesis

Methylation analysis of 79 patients with growth restriction reveals novel patterns of methylation change at imprinted loci

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