Home About us Contact
|
Home About us Contact | ||
|
|
||
Wilms Tumor Gene (Wilm + tumor_gene)
Selected AbstractsWilms tumor genetics: Mutations in WT1, WTX, and CTNNB1 account for only about one-third of tumorsGENES, CHROMOSOMES AND CANCER, Issue 6 2008E. Cristy Ruteshouser Wilms tumor is genetically heterogeneous, and until recently only one Wilms tumor gene was known, WT1 at 11p13. However, WT1 is altered in only ,20% of Wilms tumors. Recently a novel gene, WTX at Xq11.1, was reported to be mutated in Wilms tumors. No overlap between tumors with mutations in WTX and WT1 was noted, suggesting that WT1 and WTX mutations could account for the genetic basis of roughly half of Wilms tumors. To assess the frequency of WTX mutations and their relationship to WT1 mutations in a larger (n = 125) panel of Wilms tumors which had been thoroughly assessed for mutations in WT1, we conducted a complete mutational analysis of WTX that included sequencing of the entire coding region and quantitative PCR to identify deletions of the WTX gene. Twenty-three (18.4%) tumors carried a total of 24 WTX mutations, a lower WTX mutation frequency than that previously observed. Surprisingly, we observed an equivalent frequency of WTX mutations in tumors with mutations in either or both WT1 and CTNNB1 (20.0%) and tumors with no mutation in either WT1 or CTNNB1 (17.5%). WTX has been reported to play a role in the WNT/,-catenin signaling pathway, and, interestingly, WTX deletion/truncation mutations appeared to be rare in tumors carrying exon 3 mutations of CTNNB1, encoding ,-catenin. Our findings indicate that WT1 and WTX mutations occur with similar frequency, that they partially overlap in Wilms tumors, and that mutations in WT1, WTX, and CTNNB1 underlie the genetic basis of about one-third of Wilms tumors. © 2008 Wiley-Liss, Inc. [source] Prognostic significance of Wilms tumor gene (WT1) mRNA expression in soft tissue sarcomaCANCER, Issue 10 2006Tsukasa Sotobori M.D. Abstract BACKGROUND There have been several recent reports that Wilms tumor gene (WT1) mRNA is overexpressed in many types of neoplasms, and those results suggested that WT1 has oncogenic properties. The objective of the current study was to evaluate the prognostic significance of WT1 mRNA expression in patients with soft tissue sarcoma. METHODS Levels of WT1 mRNA expression were examined by quantitative, real-time reverse transcriptase-polymerase chain reaction analysis in frozen tissue samples from 52 patients with soft tissue sarcoma. Various clinicopathologic factors were analyzed along with the disease-specific survival rate for correlations with WT1 mRNA expression levels. RESULTS The levels of WT1 mRNA expression in a variety of soft tissue sarcomas were significantly greater compared with the levels in normal soft tissue samples (P = .0212). No significant correlation was observed between the level of WT1 mRNA expression and clinicopathologic factors, including gender, age, primary tumor site, tumor depth, tumor size, histologic grade, and distant metastasis at initial presentation. The disease-specific survival rate for patients with high WT1 mRNA expression levels was found significantly poorer compared with the rate for patients with low WT1 mRNA expression levels (P = .0182). Moreover, multivariate analysis indicated that a high WT1 mRNA expression level was an independent, adverse prognostic factor for disease-specific survival (hazards ratio, 2.6; P = .0488). CONCLUSIONS WT1 mRNA expression level can serve as a potent prognostic indicator in soft tissue sarcoma patients. Cancer 2006. © 2006 American Cancer Society. [source] Desmoplastic small round cell tumor: Using FISH as an ancillary technique to support cytologic diagnosis in an unusual caseDIAGNOSTIC CYTOPATHOLOGY, Issue 8 2007Michael S. Waugh M.D. Abstract Desmoplastic small round cell tumor is a rare and aggressive neoplasm that predominantly affects young males. In almost all cases, a reciprocal translocation is present resulting in the fusion of the Ewing sarcoma gene with the Wilms' tumor gene. Here we describe an unusual case occurring in a 59-year-old male, in which fluorescence in situ hybridization (FISH) was used in conjunction with immunohistochemical studies to confirm the diagnosis. To our knowledge, this is the first reported case of using FISH as an ancillary technique to confirm the cytologic diagnosis of this tumor. Diagn. Cytopathol. 2007;35:516,520. © 2007 Wiley-Liss, Inc. [source] Characteristics of testicular dysgenesis syndrome and decreased expression of SRY and SOX9 in Frasier syndromeMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 9 2008Valérie Schumacher Abstract Frasier syndrome (FS) is characterized by chronic renal failure in early adulthood, varying degrees of gonadal dysgenesis, and a high risk for gonadal germ cell malignancies, particularly gonadoblastoma. Although it is known to arise from heterozygous splice mutations in intron 9 of the Wilms' tumor gene 1 (WT1), the mechanisms by which these mutations result in gonadal dysgenesis in humans remain obscure. Here we show that a decrease in WT1,+,KTS isoforms due to disruption of alternative splicing of the WT1 gene in a FS patient is associated with diminished expression of the transcription factors SRY and SOX9 in Sertoli cells. These findings provide the first confirmation in humans of the results obtained by others in mice. Consequently, Sertoli cells fail to form the specialized environment within the seminiferous tubules that normally houses developing germ cells. Thus, germ cells are unable to fully mature and are blocked at the spermatogonial,spermatocyte stage. Concomitantly, subpopulations of the malignant counterpart of primordial germ cells/gonocytes, the intratubular germ cell neoplasia unclassified type (ITGCN), are identified. Furthermore, dysregulated Leydig cells produce insufficient levels of testosterone, resulting in hypospadias. Collectively, the impaired spermatogenesis, hypospadias and ITGCN comprise part of the developmental disorder known as ,testicular dysgenesis syndrome' (TDS), which arises during early fetal life. The data presented here show that critical levels of WT1,+,KTS, SRY and SOX9 are required for normal Sertoli cell maturation, and subsequent normal spermatogenesis. To further study the function of human Sertoli cells in the future, we have established a human cell line. Mol. Reprod. Dev. 75: 1484,1494, 2008. © 2008 Wiley-Liss, Inc. [source] | ||||||||||