Upregulation of Wilms' tumor gene 1 (<i>WT1</i>) in desmoid tumors

Amini-Nik, Saeid; Hohenstein, Peter; Jadidizadeh, Ali; Dam, Kim Van; Bastidas, Adriana; Berry, Rachel L.; Patek, Charles E.; Schueren, B Van der; Cassiman, Jean‐Jacques; Tejpar, Sabine

doi:10.1002/ijc.20717

Cited by 38 publications

(20 citation statements)

References 27 publications

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“…WT1 is a well-known tumor suppressor gene in Wilms' tumor (26). However, data have accumulated regarding an oncogenic role for WT1 in various adult tumors, including colorectal (36), breast (37), desmoid (38), pancreatic (39) and brain tumors (40). The bi-directional control of the mesenchymal-epithelial transition (41,42) may partially explain how WT1 is able to function as a tumor suppressor gene in some tissues and as a potential oncogene in others.…”

Section: Discussionmentioning

confidence: 99%

WT1-associated protein is a novel prognostic factor in pancreatic ductal adenocarcinoma

Huang

Shao

et al. 2017

Oncology Letters

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Although Wilms tumor 1 (WT1)-associated protein (WTAP) was initially found to be a specific WT1-binding protein, it has increasingly attracted attention because of its oncogenic role in various types of malignancies, including cholangiocarcinoma, glioblastoma and acute myeloid leukemia. However, the clinical impact of WTAP on pancreatic ductal adenocarcinoma (PDAC) is still unknown. A total of 145 patients who underwent surgical treatment from 2004 to 2008 were enrolled in the present study. The cytoplasmic and nuclear expression of WTAP in tumor and adjacent normal tissues was examined by immunohistochemical analysis in order to investigate the relationship between WTAP and the clinicopathological factors and prognosis of patients with PDAC. The nuclear and cytoplasmic expression of WTAP in tumor tissues was significantly higher compared with non-tumor tissues (P<0.001). High expression of WTAP in the nucleus was significantly associated with gender (P=0.010) and tumor stage (P=0.020), while high expression of WTAP in the cytoplasm was significantly associated with gender (P=0.018), histological grade (P=0.047) and perineural invasion (P=0.028). In addition, a univariate analysis revealed that high nuclear expression of WTAP in tumor tissues was significantly associated with poor overall survival (P<0.001), as well as several clinicopathological variables, including gender and N stage. In a multivariate Cox regression analysis, nuclear WTAP expression was identified as an independent prognostic indicator for PDAC (relative risk, 1.855; 95% confidence interval, 1.033–3.333; P=0.039). The results of the present study indicated that high nuclear expression of WTAP is a valuable molecular biomarker of a poor prognosis among patients with PDAC.

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Section: Discussionmentioning

confidence: 99%

WT1-associated protein is a novel prognostic factor in pancreatic ductal adenocarcinoma

Huang

Shao

et al. 2017

Oncology Letters

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“…These include transcriptional activation and repression (77); roles in RNA processing and translation (73,78,79); localization in nucleus or cytoplasm (80–82); a tumor suppressor in the formation of Wilms tumor, and an oncogene in adult tumors (83–86); a role in controlling active (H3K4me3) and repressive (H3K27me3) histone modification marks (87); and a capacity to differentially bind to epigenetically modified DNA (29). WT1 is expressed in cells that are undergoing epithelial-to-mesenchymal transition (88–90) or the reverse, mesenchymal-to-epithelial transition (87,91).…”

Section: Discussionmentioning

confidence: 99%

Denys-Drash syndrome associated WT1 glutamine 369 mutants have altered sequence-preferences and altered responses to epigenetic modifications

Hashimoto

Zhang

Zheng³

et al. 2016

Nucleic Acids Res

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Mutations in human zinc-finger transcription factor WT1 result in abnormal development of the kidneys and genitalia and an array of pediatric problems including nephropathy, blastoma, gonadal dysgenesis and genital discordance. Several overlapping phenotypes are associated with WT1 mutations, including Wilms tumors, Denys-Drash syndrome (DDS), Frasier syndrome (FS) and WAGR syndrome (Wilms tumor, aniridia, genitourinary malformations, and mental retardation). These conditions vary in severity from individual to individual; they can be fatal in early childhood, or relatively benign into adulthood. DDS mutations cluster predominantly in zinc fingers (ZF) 2 and 3 at the C-terminus of WT1, which together with ZF4 determine the sequence-specificity of DNA binding. We examined three DDS associated mutations in ZF2 of human WT1 where the normal glutamine at position 369 is replaced by arginine (Q369R), lysine (Q369K) or histidine (Q369H). These mutations alter the sequence-specificity of ZF2, we find, changing its affinity for certain bases and certain epigenetic forms of cytosine. X-ray crystallography of the DNA binding domains of normal WT1, Q369R and Q369H in complex with preferred sequences revealed the molecular interactions responsible for these affinity changes. DDS is inherited in an autosomal dominant fashion, implying a gain of function by mutant WT1 proteins. This gain, we speculate, might derive from the ability of the mutant proteins to sequester WT1 into unproductive oligomers, or to erroneously bind to variant target sequences.

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“…WT1 expression in the adult kidney appears to be limited to the podocytes and, although functioning as a tumour suppressor in the formation of Wilms' tumour, it is becoming increasingly clear that WT1 is expressed in a variety of adult tumours from various origins where it is not normally expressed, including carcinomas of the lung [14], colon [15] and pancreas [16], as well as breast [17], desmoid [18] and brain tumours [19]. Since no mutations have been identified in the WT1 gene, it has been suggested that WT1 might function as an oncogene in these tumours (reviewed in [20]).…”

Section: Wt1 a Candidate Oncogenementioning

confidence: 99%

The role of the Wilms' tumour-suppressor protein WT1 in apoptosis

Hartkamp

Roberts

2008

Biochemical Society Transactions

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The Wilms' tumour-suppressor gene (WT1), encodes a zinc-finger transcription factor that is critical for the development of several organs, including the kidneys, gonads and spleen. Despite its identification as a tumour suppressor that plays a crucial role in the formation of a paediatric malignancy of the kidneys (Wilms' tumour), it has also emerged as an oncogenic factor influencing proliferation and apoptosis in a large variety of adult cancers. This review focuses on new insights into WT1's role in early development and its potential oncogenic role in adult cancer.

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Upregulation of Wilms' tumor gene 1 (WT1) in desmoid tumors

Cited by 38 publications

References 27 publications

WT1-associated protein is a novel prognostic factor in pancreatic ductal adenocarcinoma

WT1-associated protein is a novel prognostic factor in pancreatic ductal adenocarcinoma

Denys-Drash syndrome associated WT1 glutamine 369 mutants have altered sequence-preferences and altered responses to epigenetic modifications

The role of the Wilms' tumour-suppressor protein WT1 in apoptosis

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