Loss of imprinting of IGF2 is linked to reduced expression and abnormal methylation of H19 in Wilms' tumour

Steenman, Marja; Rainier, Shirley; Dobry, Craig J.; Grundy, Paul E.; Horon, Isabelle L.; Feinberg, Andrew P.

doi:10.1038/ng0794-433

Cited by 432 publications

(299 citation statements)

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“…The present data also show that allelic expression patterns of H19 and IGF2 in TGCTs are different from other type of neoplasms (Moulton et al, 1994;Steenman et al, 1994;Taniguchi et al, 1995;Cui et al, 2001;Nakagawa et al, 2001;Ulaner et al, 2003): null expression, monoallelic expression and biallelic expression of both H19 and IGF2 were observed in TGCTs with consistent unmethylated DNA profiles of H19 (Table 1). Biallelic expression of both IGF2 and H19 has been reported in TGCTs of adolescents (van Gurp et al, 1994;Nonomura et al, 1997;Verkerk et al, 1997) and pediatrics (Ross et al, 1999).…”

Section: T Kawakami Et Alsupporting

confidence: 65%

“…The common expression patterns in TGCTs were biallelic expression of H19 and null expression of IGF2 in the present study (Table 1). The patterns of H19/IGF2 expression were in contrast to those in Wilms' tumors (Ogawa et al, 1993;Rainier et al, 1993;Moulton et al, 1994;Steenman et al, 1994;Taniguchi et al, 1995;Feinberg and Tycko, 2004).…”

Section: T Kawakami Et Almentioning

confidence: 69%

“…Epigenetic alterations in the 11p15.5 imprinted gene cluster are frequent in human cancers and are associated with disordered imprinting of IGF2 and H19 (Ogawa et al, 1993;Rainier et al, 1993;Moulton et al, 1994;Steenman et al, 1994;Taniguchi et al, 1995;Feinberg and Tycko, 2004). Loss of imprinting leads to pathological biallelic expression of IGF2 in Wilms' tumors (Ogawa et al, 1993;Rainier et al, 1993).…”

Section: T Kawakami Et Almentioning

confidence: 99%

“…Loss of imprinting leads to pathological biallelic expression of IGF2 in Wilms' tumors (Ogawa et al, 1993;Rainier et al, 1993). This abnormality in Wilms' tumors is inevitably linked to a gain in methylation, localized to the 5 0 sequences and transcribed region of the closely linked and reciprocally imprinted H19 gene (Moulton et al, 1994;Steenman et al, 1994;Taniguchi et al, 1995). Recently, the methylation status of the binding site of insulator protein, CTCF, in the upstream region of H19 has been suggested to be critical in the regulation of the H19/IGF2 locus (Bell and Felsenfeld, 2000;Hark et al, 2000).…”

Section: T Kawakami Et Almentioning

confidence: 99%

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Erasure of methylation imprint at the promoter and CTCF-binding site upstream of H19 in human testicular germ cell tumors of adolescents indicate their fetal germ cell origin

et al. 2006

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Genome-wide epigenetic modification plays a crucial role in regulating genome functions at critical stages of development. In particular, DNA methylation is known to be reprogrammed on a genome-wide level in germ cells and in preimplantation embryos, although it is relatively stable in somatic cells. In this reprogramming process, the genome becomes demethylated, and methylated de novo during later stages of development. Reprogramming of DNA methylation in male germ cells has not been fully investigated. Testicular germ cell tumors (TGCTs) possess a pluripotential nature and display protean histology from germ cells to embryonal and somatic cell differentiation. These properties make TGCT a unique model for studying germ cell development and gametogenesis in respect of DNA reprogramming. In order to obtain an insight into the epigenetic dynamics of TGCTs, we conducted a comprehensive analysis of differential methylated regions (DMRs) on H19 and IGF2 in TGCTs compared with testicular malignant lymphomas. In the present study, we show that methylation imprint at the promoter and CTCF-binding site upstream of H19 was completely erased in both seiminomatous and nonseminomatous TGCTs, whereas differential methylation was observed in testicular lymphomas. The erasure of methylation imprint was also observed in TGCTs with malignant transformation. We found biallelic unmethylation at the promoter and the CTCF-binding site upstream of H19 is required, but not sufficient for the biallelic expression of H19 in TGCTs. These data suggest that factors other than methylation contribute to transcriptional regulation of imprinted genes in TGCTs. The present data have shown that TGCTs carry distinctive epigenetic profiles at the core-imprinting domain of H19/ IGF2 from other neoplasms of somatic cell origin. The data also suggest that both seminomatous and nonseminomatous TGCTs carry methylation profiles similar to fetal germ cells, but not adult germ cells, indicating the origin of TGCTs as fetal germ cells.

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Section: T Kawakami Et Alsupporting

confidence: 65%

Section: T Kawakami Et Almentioning

confidence: 69%

Section: T Kawakami Et Almentioning

confidence: 99%

Section: T Kawakami Et Almentioning

confidence: 99%

See 2 more Smart Citations

Erasure of methylation imprint at the promoter and CTCF-binding site upstream of H19 in human testicular germ cell tumors of adolescents indicate their fetal germ cell origin

et al. 2006

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“…Although de novo methylation and silencing of H19 in Wilms' tumours was first reported some years ago (Steenman et al, 1994;Taniguchi et al, 1995), epigenetic changes have not been investigated in great detail in Wilms' tumour. Recently, we reported frequent CASP8 (43%) and RASSF1A (56%) promoter methylation in Wilms' tumours and the present study has demonstrated that SLIT2 methylation represents a further frequent epigenetic change in Wilms' tumours.…”

Section: Discussionmentioning

confidence: 99%

SLIT2 promoter methylation analysis in neuroblastoma, Wilms' tumour and renal cell carcinoma

et al. 2004

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The 3p21.3 RASSF1A tumour suppressor gene (TSG) provides a paradigm for TSGs inactivated by promoter methylation rather than somatic mutations. Recently, we identified frequent promoter methylation without somatic mutations of SLIT2 in lung and breast cancers, suggesting similarities between SLIT2 and RASSF1A TSGs. Epigenetic inactivation of RASSF1A was first described in lung and breast cancers and subsequently in a wide range of human cancers including neuroblastoma, Wilms' tumour and renal cell carcinoma (RCC). These findings prompted us to investigate SLIT2 methylation in these three human cancers. We analysed 49 neuroblastomas (NBs), 37 Wilms' tumours and 48 RCC, and detected SLIT2 promoter methylation in 29% of NB, 38% of Wilms' tumours and 25% of RCC. Previously, we had demonstrated frequent RASSF1A methylation in the same tumour series and frequent CASP8 methylation in the NB and Wilms' tumour samples. However, there was no significant association between SLIT2 promoter methylation and RASSF1A or CASP8 methylation in NB and RCC. In Wilms' tumour, there was a trend for a negative association between RASSF1A and SLIT2 methylation, although this did not reach statistical significance. No associations were detected between SLIT2 promoter methylation and specific clinicopathological features in the tumours analysed. These findings implicate SLIT2 promoter methylation in the pathogenesis of both paediatric and adult cancers and suggest that further investigations of SLIT2 in other tumour types should be pursued. However, epigenetic inactivation of SLIT2 is less frequent than RASSF1A in the tumour types analysed.

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Imprinting is also a mechanism for immediate or delayed hemizygous expression of several uniparental haplotypes selected from the genome of each sex

Engel

1997

Am. J. Med. Genet.

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A peculiar and interesting aspect of monoallelic or hemizygous expression, resulting from genomic imprinting, should be a likeness or resemblance for some phenotypic traits between relatives inheriting identical active genes or domains. Although the word "likon," a neologism, is reminiscent of the above implication, it is here proposed for use in a broader sense, namely, to designate a haplotype or part of a haplotype of an imprinted domain. As learned from earlier studies of imprinting and uniparental disomies, haplotypes at loci of such domains may be expressed (E) or unexpressed (U) in somatic cells; they may also be transmitted to be expressed or not in the next generation by germ cells "acting" (A) or marked to be "resting" (R) for such loci. Thus the soma/germinal status of "likons" might for each genitor be abbreviated as EA, UA, ER, and UR. In an evolutionary sense the assumption is that the same monoallelically expressed loci and domains when carried by two or more relatives should be the source of identical transcripts contributing to a closely similar phenotype. If so, the overall phenotype would be distinct if arising from some 10 to 20 imprinted genes or domains potentially gaining expression from the germ cells of either one or the other sex in humans. The result may have evolutionary implications by narrowing the scope of random individual variation and by strengthening assortative and associative values (physical, behavioral, and instinctual) in one's own lineage and species.

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Loss of imprinting of IGF2 is linked to reduced expression and abnormal methylation of H19 in Wilms' tumour

Cited by 432 publications

References 49 publications

Erasure of methylation imprint at the promoter and CTCF-binding site upstream of H19 in human testicular germ cell tumors of adolescents indicate their fetal germ cell origin

Erasure of methylation imprint at the promoter and CTCF-binding site upstream of H19 in human testicular germ cell tumors of adolescents indicate their fetal germ cell origin

SLIT2 promoter methylation analysis in neuroblastoma, Wilms' tumour and renal cell carcinoma

Imprinting is also a mechanism for immediate or delayed hemizygous expression of several uniparental haplotypes selected from the genome of each sex

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