Human p57KIP2 defines a new imprinted domain on chromosome 11p but is not a tumour suppressor gene in Wilms tumour

Taniguchi, Tadatsugu; Okamoto, Keigo; Reeve, Anthony E.

doi:10.1038/sj.onc.1200934

Cited by 45 publications

(32 citation statements)

References 30 publications

(45 reference statements)

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“…Although KIP2 expression is epigenetically reduced in several adult tumours (Shin et al, 2000;Kikuchi et al, 2002;Li et al, 2002;Soejima et al, 2004), expression levels in Wilms' tumour as measured in previous studies have varied (Chung et al, 1996;Hatada et al, 1996;Thompson et al, 1996;O'Keefe et al, 1997;Taniguchi et al, 1997;. In the present study, KIP2 expression also varied, suggesting that at least in Wilms' tumour, KIP2 may not be involved.…”

Section: Discussionsupporting

confidence: 40%

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Genetic and epigenetic alterations on the short arm of chromosome 11 are involved in a majority of sporadic Wilms' tumours

et al. 2006

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Wilms' tumour is one of the most common solid tumours of childhood. 11p13 (WT1 locus) and 11p15.5 (WT2 locus) are known to have genetic or epigenetic aberrations in these tumours. In Wilms' tumours, mutation of the Wilms tumour 1 (WT1) gene at the WT1 locus has been reported, and the WT2 locus, comprising the two independent imprinted domains IGF2/H19 and KIP2/LIT1, can undergo maternal deletion or alterations associated with imprinting. Although these alterations have been identified in many studies, it is still not clear how frequently combined genetic and epigenetic alterations of these loci are involved in Wilms' tumours or how these alterations occur. To answer both questions, we performed genetic and epigenetic analyses of these loci, together with an additional gene, CTNNB1, in 35 sporadic Wilms' tumours. Loss of heterozygosity of 11p15.5 and loss of imprinting of IGF2 were the most frequent genetic (29%) and epigenetic (40%) alterations in Wilms' tumours, respectively. In total, 83% of the tumours had at least one alteration at 11p15.5 and/or 11p13. One-third of the tumours had alterations at multiple loci. Our results suggest that chromosome 11p is not only genetically but also epigenetically critical for the majority of Wilms' tumours.

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Section: Discussionsupporting

confidence: 40%

“…In several adult tumours, KIP2 expression is epigenetically reduced (Shin et al, 2000;Kikuchi et al, 2002;Li et al, 2002;Soejima et al, 2004). However, KIP2 expression has been found to be reduced in Wilms' tumours in some studies, but not in others (Chung et al, 1996;Hatada et al, 1996;Thompson et al, 1996;O'Keefe et al, 1997;Taniguchi et al, 1997;.…”

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confidence: 99%

Genetic and epigenetic alterations on the short arm of chromosome 11 are involved in a majority of sporadic Wilms' tumours

et al. 2006

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“…These results showed that the levels of p16 Ink4a and p57 Kip2 , two inhibitors that belong to di erent families of CKIs, were elevated at the same stage during mouse skin papilloma development. It is noteworthy to mention that p16 Ink4a is the product of a tumor suppressor gene that is mutated in several varieties of cancers (Hirama and Koe er, 1995), and the p57 Kip2 gene is in a region of human chromosome 11 implicated in Beckwith-Wiedermann syndrome (Taniguchi et al, 1997). On the other hand, p21 Cip1 and p27 Kip1 have not yet been implicated in tumorigenesis.…”

Section: Expression Of Ckismentioning

confidence: 99%

Deregulated expression of cell-cycle proteins during premalignant progression in SENCAR mouse skin

et al. 1998

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It is now evident that several genes encoding regulatory activities that control the mammalian cell cycle, particularly some that control the progression of quiescent cells through G1 and into S phase, are targets for alterations that underlie the development of neoplasms. Here, we made a sequential study of alterations in cell cycle protein expression and complex formation among cyclin, cyclin dependent kinases (CDKs) and CDK inhibitors (CKIs) during premalignant progression in SENCAR mouse skin tumors. Changes in the level of expression were observed in positive (cyclin D1, D2, and E2F family members) and negative regulators (p16 Ink4a , p57 Kip2 ) of the cell cycle. Also, we observed the formation of cyclin/CDK/CKI complexes. The amounts of these proteins and complexes increased substantially at speci®c times during promotion but not during malignant conversion to carcinomas. These data show that deregulation of growth control occurs in benign tumors and that subsequent mutations not involved cell-cycle regulation are probably necessary to induce invasive behavior.

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“…Support for this comes from the phenotypic differences that are observed in different groups of Beckwith-Wiedemann syndrome patients, depending on whether they have IC1 and/or IC2 defects (36). However, imprinting of human CDKN1C is incomplete in some tissues and the normally less active paternal allele can be expressed in 11p15 LOH WTs, so that often there is no significant difference in CDKN1C expression between LOH and heterozygous WTs (42)(43)(44). This suggests that if the expression of 11p15 IC2-regulated imprinted genes is responsible for the phenotypic differences between LOH and LOI tumors, then other genes apart from CDKN1C are more likely to be responsible; some have already been shown to have altered expression in WT (8).…”

Section: Loi At 11p15mentioning

confidence: 99%

Frequency and Timing of Loss of Imprinting at 11p13 and 11p15 in Wilms' Tumor Development

Brown

Power

Moore

et al. 2008

Molecular Cancer Research

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Epigenetic changes occur frequently in Wilms' tumor (WT), especially loss of imprinting (LOI) of IGF2/H19 at 11p15. Our previous results have identified imprinted transcripts (WT1-AS and AWT1) from the WT1 locus at 11p13 and showed LOI of these in some WTs. In this article, we set out to test the relationship between LOI at 11p13 and 11p15 and their timing in WT progression relative to other genetic changes. We found a higher level (83%) of 11p13 LOI in WT than of 11p15 LOI (71%). There was no correlation between methylation levels at the 11p13 and 11p15 differentially methylated regions or between allelic expression of WT1-AS/AWT1 and IGF2. Interestingly, retention of normal imprinting at 11p13 was associated with a small group of relatively late-onset, high-stage WTs. An examination of genetic and epigenetic alterations in nephrogenic rests, which are premalignant WT precursors, showed that LOI at both 11p13 and 11p15 occurred before either 16q loss of heterozygosity (LOH) or 7p LOH. This suggests that these LOH events are very unlikely to be a cause of LOI but that LOH may act by potentiating the effects of overexpression of IGF2 and/or WT1-AS/AWT1 that

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Human p57KIP2 defines a new imprinted domain on chromosome 11p but is not a tumour suppressor gene in Wilms tumour

Cited by 45 publications

References 30 publications

Genetic and epigenetic alterations on the short arm of chromosome 11 are involved in a majority of sporadic Wilms' tumours

Genetic and epigenetic alterations on the short arm of chromosome 11 are involved in a majority of sporadic Wilms' tumours

Deregulated expression of cell-cycle proteins during premalignant progression in SENCAR mouse skin

Frequency and Timing of Loss of Imprinting at 11p13 and 11p15 in Wilms' Tumor Development

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