Epigenetic differences between Wilms' tumours in white and east-Asian children

Fukuzawa, Ryuji; Breslow, Norman E.; Morison, Ian M.; Dwyer, Patrick; Kusafuka, Takeshi; Kobayashi, Yasutsugu; Becroft, D. M. O.; Beckwith, J. Bruce; Perlman, Elizabeth J.; Reeve, Anthony E.

doi:10.1016/s0140-6736(04)15491-3

Cited by 73 publications

(83 citation statements)

References 23 publications

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“…(26,27) While ILNRs and PLNRs were found in 20% and 17%, respectively, of Caucasians with WTs, the incidence rates were 25% and 2%, respectively, in Japanese with WTs. (5) WTs in the present and previous series were classified into three types based on IGF2 status, and are summarized in Table 3. Yuan et al identified IGF2 LOI in 37.9% of 58 sporadic WTs, and their frequency is lower than that of IGF2 LOI in the present series of 101 sporadic WTs (P = 0.04) ( Table 3).…”

Section: Discussionmentioning

confidence: 99%

“…There have been conflicting reports on the rates of IGF2 LOI in Japanese with WTs; one study reported IGF2 LOI in none of 21 tumors, whereas we previously reported it in seven of 27 tumors. (5,6) These results prompted us to analyze the IGF2 imprinting status in a substantial number of Japanese children with WTs.Various abnormalities of the WT1 gene have been found in 13.0-17.6% of sporadic WTs. (7,8) WT1 is predominantly expressed in the embryonic kidney, and has a pivotal role in its development.…”

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Different incidences of epigenetic but not genetic abnormalities between Wilms tumors in Japanese and Caucasian children

et al. 2012

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Epidemiological studies show that the incidence of Wilms tumor (WT) in East-Asian children is half of that in Caucasian children. Abnormalities of WT1, CTNNB1, WTX, and IGF2 were reported to be involved in Wilms tumorigenesis in Caucasians, although none of the studies simultaneously evaluated the four genes. WTX forms the b-catenin degradation complex; however, the relationship between WTX abnormality and CTNNB1 mutation was uncertain in WTs. We examined abnormalities of the four genes in 114 Japanese with WTs to clarify the relationship between genetic and epigenetic factors and the incidence of WTs. We found that abnormalities of WTX and CTNNB1 were mutually exclusive, and that although CTNNB1 mutation was frequent in WTs with WT1 abnormality, but rare in WTs without, the incidences of WTX abnormality were similar between WTs with or without WT1 abnormality. These findings were consistent with those reported in Caucasian populations, and indicate multiple roles of WTX abnormality. Abnormalities of WT1, WTX and CTNNB1, and loss of IGF2 imprinting (LOI) were detected in 31.6%, 22.8%, 26.3%, and 21.1% of the 114 WTs, respectively. When we selected 101 sporadic WTs, the incidences of WT1, CTNNB1, or WTX abnormality were generally comparable between the two populations, whereas the incidence of IGF2 LOI was lower in Japanese than that of IGF2 LOI reported in Caucasians (P = 0.04). This is the first comprehensive study of the four genes, and the results supported the hypothesis that the lower incidence of IGF2 LOI contributes to the lower incidence of WTs in Japanese children. (Cancer Sci 2012; 103: 1129-1135 T he rates of various types of adult cancers, including prostate, lung, breast, liver and gastric cancers, differ among ethnic populations, which are thought to be caused by different environmental factors. (1) In contrast, most pediatric tumors such as neuroblastomas and retinoblastomas show similar rates among ethnic populations. An exception is Wilms tumor (WT), a common pediatric tumor of the kidney, which is known to have different incidence rates between East-Asian and Caucasian populations. (2) Wilms tumor accounts for 8% of childhood cancers and occurs in 1 in 10 000 Caucasian children, though its incidence in East-Asian populations is half of that. (2) In Hawaii and Britain, the incidence of WT in people of Asian descent is about half to two-thirds of that in Caucasians, (3,4) suggesting that environmental factors play little part in the lower incidence.IGF2 is an imprinting gene expressed from the paternally inherited allele, and encodes a fetal polypeptide growth factor. Loss of imprinting (LOI) of IGF2 has been reported in various tumors, including pediatric tumors. There have been conflicting reports on the rates of IGF2 LOI in Japanese with WTs; one study reported IGF2 LOI in none of 21 tumors, whereas we previously reported it in seven of 27 tumors. (5,6) These results prompted us to analyze the IGF2 imprinting status in a substantial number of Japanese children with WTs.Various abnormalities of...

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Section: Discussionmentioning

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confidence: 99%

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Different incidences of epigenetic but not genetic abnormalities between Wilms tumors in Japanese and Caucasian children

et al. 2012

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“…In addition to our data set of WNT target genes (Table 2a), we compiled all differentially expressed As previously reported by Fukuzawa et al (2004b). b As previously reported by Fukuzawa et al (2007).…”

Section: Unsupervised Clustering Analysis Of Wts Using Wnt Target Genesmentioning

confidence: 99%

“…We examined 59 WTs for WT1 mutations, 11p13 LOH, 11p15 LOH, imprinting status of IGF2 and CTNNB1 mutations (exons 3, 7 and 8) as previously described (Ogawa et al, 1993;Fukuzawa et al, 2004aFukuzawa et al, , 2004bFukuzawa et al, , 2008. Previously published cases are listed in Table 2a.…”

Section: Wt1 Ctnnb1 Mutations Igf2 Imprinting and 11p Loh Analysismentioning

confidence: 99%

Canonical WNT signalling determines lineage specificity in Wilms tumour

et al. 2009

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Wilms tumours (WTs) have two distinct types of histology with or without ectopic mesenchymal elements, suggesting that WTs arise from either the mesenchymal or epithelial nephrogenic lineages. Regardless of the presence or absence of CTNNB1 mutations, nuclear accumulation of b-catenin is often observed in WTs with ectopic mesenchymal elements. Here, we addressed the relationship between the WNT-signalling pathway and lineage in WTs by examining CTNNB1 and WT1 mutations, nuclear accumulation of b-catenin, tumour histology and gene expression profiles. In addition, we screened for mutations in WTX, which has been proposed to be a negative regulator of the canonical WNT-signalling pathway. Unsupervised clustering analysis identified two classes of tumours: mesenchymal lineage WNT-dependent tumours, and epithelial lineage WNT-independent tumours. In contrast to the mesenchymal lineage specificity of CTNNB1 mutations, WTX mutations were surprisingly observed in both lineages. WTX-mutant WTs with ectopic mesenchymal elements had nuclear accumulation of b-catenin, upregulation of WNT target genes and an association with CTNNB1 mutations in exon 7 or 8. However, epithelial lineage WTs with WTX mutations had no indications of active WNT signalling, suggesting that the involvement of WTX in the WNT-signalling pathway may be lineage dependent, and that WTX may have an alternative function to its role in the canonical WNT-signalling pathway.

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