Disease relevance of WIT1

• These results suggest that expression patterns of the WT1 and WIT1 genes can be closely correlated to Wilms' tumor histopathology [1].
• Restriction landmark genome scanning for aberrant methylation in primary refractory and relapsed acute myeloid leukemia; involvement of the WIT-1 gene [2].
• Since the erythropoietin hormone assayed in these and other Wilms tumor patients was not associated with polycythemia, it is believed that Wilms tumor-associated erythropoietin differs in some manner from the hormone produced normally in man and possible in other states associated with secondary polycythemia [3].
• A case of Wilms tumor associated with hydronephrosis is reported [4].
• Sarcomatous Wilms tumor associated with consumption coagulopathy [5].

High impact information on WIT1

• Complementary DNA clones representing transcripts of 2.5 (WIT-1) and 3.5 kb (WIT-2) mapping to this region were isolated from a kidney complementary DNA library [6].
• However, seven of eight (87.5%) diagnostic BM samples from primary refractory AML (chemosensitive) showed methylation of WIT-1 [2].
• Sequence analysis showed that the spot represented a portion of the WIT-1 gene on human chromosome 11p13 [2].
• Rp18 was missing in the relapse sample due to a distinct DNA methylation pattern of the WIT-1 gene [2].
• Twenty-seven AML patients that entered CR after therapy (i.e., chemosensitive) were studied and only 10 (37%) of the diagnostic bone marrow (BM) samples showed methylation of WIT-1 [2].

Biological context of WIT1

• The other transcript, WIT1, encodes a product of unknown function that is subject to alternate splicing in the region immediately 5' of the WT1 gene [7].
• In one case this was coincident with reduction of WT1 and WIT1 gene expression, and in 3 other cases it occurred in addition to 11p LOH [8].
• The cloning and molecular characterization of two putative tumor genes, WT1 and WIT1, from the chromosome 11p13 region has provided a means of evaluating their role in the generation of Wilms' tumor heterogeneity [1].
• We conclude that SNPs in WT1 and WIT1 genes are significantly associated with FSGS, suggesting that variants in these genes may mediate pathogenesis by altering WT1 function [9].
• Wit1 promoter activity was identified in a DNA fragment extending from 200 bp upstream of the putative Wit1 TATA box to 130 bp downstream [10].

Anatomical context of WIT1

• WT1 and Wit1 promoter activities were tested in COS-7 cells with luciferase reporter gene constructs either containing or lacking an SV40 enhancer [10].

Other interactions of WIT1

• RNase protection revealed divergent transcription of WIT-1 and WIT-2, originating from a DNA region of less than 600 bp [6].
• We particularly show that 25% of modulated genes concern signal transduction and trafficking, that the calcium pathway is heavily disturbed and that nephroblastomas-related genes are involved (WIT-1, STMN1, and STMN2) [11].
• Wilms tumor associated with elevated alpha-fetoprotein level [12].

Analytical, diagnostic and therapeutic context of WIT1

• In situ hybridization using antisense RNA probes showed that WT1 and WIT1 were concordantly expressed in normal fetal kidney and in the blastema of tumors [1].
• A series of 29 tumors were analyzed for WT1 and WIT1 expression by Northern blot or RNase protection analyses, and results were compared with tumor histopathology [1].
• To test whether genetic variations in WT1 and WIT1 (gene immediately 5' to WT1) associate with focal segmental glomerulosclerosis (FSGS), patients with biopsy-proven idiopathic and HIV-1-associated FSGS were enrolled in a multicenter study [9].

References