Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms' tumor locus

Call, Katherine M.; Gläser, Thomas; Ito, Caryn Y.; Buckler, Alan; Pelletier, Jerry; Haber, Daniel A.; Rose, Elise; Kral, Astrid M.; Yeger, Herman; Lewis, William H.; Jones, Carol; Housman, David E.

doi:10.1016/0092-8674(90)90601-a

Cited by 1,727 publications

(900 citation statements)

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“…Wilms tumor is known to have allelic loss at numerous loci (Grundy et al, , 1998Law et al, 1997;Klamt et al, 1998;Natrajan et al, 2006). One Wilms tumor gene (WT1) has been identified and mapped to 11p13 (Call et al, 1990;Gessler et al, 1990). The WT1 gene encoding a zinc-finger transcription factor is described to be mutated in 10-15% of sporadic Wilms tumors (Gessler et al, 1994;Varanasi et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

Sporadic human renal tumors display frequent allelic imbalances and novel mutations of the HRPT2 gene

et al. 2006

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Inactivation of the HRPT2 gene encoding parafibromin was recently linked to the familial hyperparathyroidismjaw tumor syndrome. Patients with this syndrome carry an increased risk of parathyroid and renal tumors. To determine the relevance of HRPT2 for sporadic renal tumors, clear cell, papillary and chromophobe renal cell carcinomas as well as oncocytomas and Wilms tumors were analysed for HRPT2 gene alterations. Loss of heterozygosity (LOH) of HRPT2 was found in seven of 56 (12.5%) clear cell, three of 14 (21%) papillary, six of 10 (60%) chromophobe renal cell carcinomas, three of eight (38%) oncocytomas and four of 10 (40%) Wilms tumors. In addition, two novel HRPT2 point mutations, causing K34Q and R292K changes in parafibromin, were detected in one clear cell carcinoma and one Wilms tumor, respectively. These tumors displayed LOH of the remaining wild-type allele, but interestingly no von HippelLindau (VHL) mutation. Functional analysis revealed that the K34Q mutant species of parafibromin is, unlike wild-type protein, defective in suppressing cyclin D1 expression in vivo. Taken together, these results suggest that renal cancer-associated mutations in parafibromin occur in the absence of VHL mutation, which in turn may contribute to constitutively elevated cyclin D1 expression and abnormal cell proliferation.

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Section: Discussionmentioning

confidence: 99%

Sporadic human renal tumors display frequent allelic imbalances and novel mutations of the HRPT2 gene

et al. 2006

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“…The WT1 tumor suppressor gene product contains four zinc ®ngers, with zinc ®ngers II-IV showing a high degree of similarity to the three EGR (early growth response)-1 zinc ®ngers (Call et al, 1990;Gessler et al, 1990). Since physiological targets of EWS/WT1 are only beginning to be evaluated (Karnieli et al, 1996), we cannot exclude the possibility that EWS/WT1 may even bind a sequence not recognized by WT1.…”

Section: Discussionmentioning

confidence: 99%

The DNA binding domains of the WT1 tumor suppressor gene product and chimeric EWS/WT1 oncoprotein are functionally distinct

1998

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The t(11; 22)(p13; q12) translocation associated with desmosplastic small round cell tumor results in a chimeric molecule fusing the amino terminal domain (NTD) of the EWS1 gene to three of the four carboxyterminal zinc ®ngers of the WT1 tumor suppressor gene. Since the DNA binding domains of WT1 and EWS/WT1 are structurally di erent, we have assessed the functional consequences of the EWS/WT1 fusion. We ®nd that the EWS/WT1 protein has a higher binding a nity for a given recognition target than the WT1 product. This is unlike other fusion products involving translocation of the NTD of EWS to DNA binding domains in which DNA binding speci®city and a nity is not changed. We demonstrate that EWS/WT1 is a nuclear protein and that the NTD of EWS contains (a) nuclear localization signal(s). We also ®nd that the integrity of a domain within the WT1 zinc ®ngers, responsible for mediating interaction between WT1 and the transcriptional repressor par-4, is disrupted in the EWS/WT1 fusion product. Deletion analysis of the NTD of EWS indicated that integrity of the entire domain was necessary to achieve full transactivation potential.

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“…[1][2][3] WT1 is arabinoside 200 mg/m 2 /day as continuous infusion days 1-7, expressed in a time-and tissue-specific manner and the WT1 n = 36); DAV (daunorubicin 45 mg/m 2 /day days 1-3, cytosine transcript is mainly expressed in the developing kidney, testis, arabinoside 2 × 100 mg/m 2 /day days 1-7, etoposide ovary, spleen and cells of hematopoietic origin. 4,5 The WT1 100 mg/m 2 /day days 1-5, n = 68). Twenty-eight of these gene consists of 10 exons, encoding a zinc finger transcription patients took part in a randomized filgrastim trial.…”

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Prognostic significance of WT1 gene expression at diagnosis in adult de novo acute myeloid leukemia

et al. 1997

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We examined the presence of WT1-specific mRNA in bone marmyeloid leukemia (AML) has been demonstrated. Several row samples of 125 patients with de novo acute myeloid leukeauthors [10][11][12][13][14][15][16][17] have shown that in the majority of AML cases mia at diagnosis by two-step RT-PCR. The sensitivity of the WT1 is expressed. In view of these findings it was of interest assay was 1:100 (first step) and 1:10 000 (second step), to see whether WT1 positivity or negativity is associated with respectively. WT1-specific mRNA was detected in 73% of specific known features of AML or might be useful as a prog- to the French-American-British (FAB) Acute Leukemia Coop-

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Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms' tumor locus

Cited by 1,727 publications

References 57 publications

Sporadic human renal tumors display frequent allelic imbalances and novel mutations of the HRPT2 gene

Sporadic human renal tumors display frequent allelic imbalances and novel mutations of the HRPT2 gene

The DNA binding domains of the WT1 tumor suppressor gene product and chimeric EWS/WT1 oncoprotein are functionally distinct

Prognostic significance of WT1 gene expression at diagnosis in adult de novo acute myeloid leukemia

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