Canonical WNT signalling determines lineage specificity in Wilms tumour

Fukuzawa, Ryuji; Anaka, Matthew; Weeks, Robert J.; Morison, Ian M.; Reeve, Anthony E.

doi:10.1038/onc.2008.455

Cited by 59 publications

(80 citation statements)

References 36 publications

(87 reference statements)

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“…(7,8,(18)(19)(20) The incidence of WT1 abnormalities in this cohort (31.6%) is much higher than that in two previous series, and comparable to that of two other series of WTs. When we included only sporadic WTs, the incidences of WT1 abnormality and CTNNB1 mutation were comparable between the present and three other series of WTs (Table 1).…”

Section: Discussionmentioning

confidence: 52%

“…(7) When tumors were classified into those with WT1 abnormalities and those without, CTNNB1 mutations were found to be more frequent in syndromic or sporadic tumors with WT1 abnormalities (P < 0.01 and P < 0.01). In contrast, WTX deletions/mutations were similarly frequent between sporadic tumors with and without WT1 abnormalities; the finding was previously reported by other investigators (Table 2).…”

Section: Resultsmentioning

confidence: 99%

“…A female tumor had a nonsense mutation (c. 1057C>T/R353X) that was previously reported in two WTs by other investigators (Table 2). (7,20) However, sequencing of cDNA from the same tumor revealed wild-type WTX mRNA expression, but not mutant WTX mRNA expression. The other single nucleotide change (c. 85G>A/A29T) was found in tumors of one male and one female, and the same change was identified in peripheral blood cells of both patients, indicating that this nucleotide conversion was of germline origin.…”

Section: Resultsmentioning

confidence: 99%

“…(16,17) Recent studies reported that WTX deletions/ mutations occur in 8-24% of WTs. (7,8,(18)(19)(20) Thus, abnormalities of all four genes, WT1, CTNNB1, WTX, and IGF2, are interrelated and implicated in the tumorigenesis of WTs. To clarify which genetic and epigenetic alterations contribute to the different incidences of WT in East-Asian and Caucasian children, and whether WTX and CTNNB1 or WT1 abnormalities coexist in WT, we performed mutational analyses in WT1, WTX and CTNNB1, and allelic expression and methylation analyses of IGF2 in 114 Japanese WTs.…”

mentioning

confidence: 99%

“…(7,8) WT1 is predominantly expressed in the embryonic kidney, and has a pivotal role in its development. We previously reported that half of 36 WTs with WT1 abnormality showed either LOI or paternal uniparental disomy (UPD) of IGF2.…”

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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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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

confidence: 52%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

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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Osteopathia striata with cranial sclerosis as a cancer predisposition syndrome: The first report of neuroblastoma and review of all cancers in OSCS

Abu‐El‐Haija,

Dillahunt,

Safina

et al. 2024

American J of Med Genetics Pt A

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Osteopathia Striata with Cranial Sclerosis (OSCS) is a rare genetic condition primarily characterized by metaphyseal striations of long bones, bone sclerosis, macrocephaly, and other congenital anomalies. It is caused by pathogenic variants in AMER1, a tumor suppressor and a WNT signaling repressor gene with key roles in tissue regeneration, neurodevelopment, tumorigenesis, and other developmental processes. While somatic AMER1 pathogenic variants have frequently been identified in several tumor types (e.g., Wilms tumor and colorectal cancer), whether OSCS (i.e., with AMER1 germline variants) is a tumor predisposition syndrome is not clear, with only nine cases reported with tumors. We here report the first case of neuroblastoma diagnosed in a male child with OSCS, review all previously reported tumors diagnosed in individuals with OSCS, and discuss potential tumorigenic mechanisms of AMER1. Our report adds to the accumulating evidence suggesting OSCS is a tumor predisposition condition, highlighting the importance of maintaining a high index of suspicion for the associated tumors when evaluating patients with OSCS. Importantly, Wilms tumor stands out as the most commonly observed tumor in OSCS patients, underscoring the need for regular surveillance.

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WNT/β‐catenin pathway activation in Wilms tumors: A unifying mechanism with multiple entries?

Corbin

Reyniès

Rickman

et al. 2009

Genes Chromosomes & Cancer

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Based on characterization of both genomic and expression status of WT1 and CTNNB1 (beta-catenin) in a series of 60 Wilms tumor samples, combined with genome-wide expression profiling of these tumors, normal mature and fetal kidney controls, we show that WT1/beta-catenin expression was a better classifier than WT1/CTNNB1 mutations. We present molecular data supporting that the WNT pathway is involved in both tumor classes, with and without WT1/beta-catenin alterations. In the tumor class with WT1/beta-catenin alterations, we identified overexpression of 14 previously unreported WNT target genes, including TWIST1. We show that the TWIST1 protein was specifically expressed in these tumors, where staining was restricted to the stromal, nuclear beta-catenin positive, component. By comparing the state of the WNT pathway in tumors without WT1/beta-catenin alterations and fetal kidneys we provide evidence that suggests that these tumors have a heightened level of pathway activation. We characterized mutations of the WNT pathway regulator gene WTX in 16% of this tumor class. Moreover, genome-transcriptome correlation analysis allowed us to identify three other WNT pathway regulator genes that could participate in the activation of the WNT pathway: BCL9 (1p36.2), CTNNBIP1 (1p36.2), and CBY1 (22q13.1). These genes thus represent new potential important actors in WT tumorigenesis.

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Canonical WNT signalling determines lineage specificity in Wilms tumour

Cited by 59 publications

References 36 publications

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

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

Osteopathia striata with cranial sclerosis as a cancer predisposition syndrome: The first report of neuroblastoma and review of all cancers in OSCS

WNT/β‐catenin pathway activation in Wilms tumors: A unifying mechanism with multiple entries?

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