| Note | |
| | |
| Entity | Wilms' tumor |
| Disease | nephroblastoma of childhood |
| Prognosis | good with treatment according to NWTS or SIOP |
| Cytogenetics | 11p13 deletions/translocations can be seen in some cases |
| Oncogenesis | up to 15% of tumors show mainly biallelic inactivation of WT1 through deletion or mutatio |
| | |
| | |
| Entity | desmoplastic small round cell tumor (DSRCT) |
| Prognosis | poor |
| Cytogenetics | translocations, t(11;22)(p13;q12) |
| Abnormal Protein | With EWS: EWS-WT; in frame fusion of EWS exons 1-7 and WT1 exons 8-10 |
| | |
| | |
| Entity | Denys-Drash syndrome (DDS) |
| Disease | defined by: mesangial sclerosis with kidney failure (age 2 yrs), gonadal dysgenesis, risk of Wilms' tumors |
| Prognosis | kidney failure at age 0-5 years |
| Hybrid/Mutated Gene | dominant negative mutations, especially missense mutations within the zinc fingers (aa 394 Arg -> Trp) but very few nonsense mutations |
| Oncogenesis | high risk of Wilms' tumor development |
| | |
| | |
| Entity | Frasier syndrome |
| Disease | defined by: complete gonadal dysgenesis, focal glomerular sclerosis, gonadoblastoma; in karyotypic females the syndrome may be limited to focal glomerular sclerosis with regular gonadal development and function |
| Prognosis | kidney failure at age 10-30 years |
| Hybrid/Mutated Gene | heterozygous point mutations of alternative splice donor site in exon 9 with imbalance of WT1 isoform ratio |
| Oncogenesis | gonadoblatoma may occur within streak gonads |
| | |
| The expression of the Wilms' tumour gene, WT1, in the developing mammalian embryo. |
| Armstrong JF, Pritchard-Jones K, Bickmore WA, Hastie ND, Bard JB |
| Mechanisms of development. 1993 ; 40 (1-2) : 85-97. |
| PMID 8382938 |
| |
| Donor splice-site mutations in WT1 are responsible for Frasier syndrome. |
| Barbaux S, Niaudet P, Gubler MC, Grünfeld JP, Jaubert F, Kuttenn F, Fékété CN, Souleyreau-Therville N, Thibaud E, Fellous M, McElreavey K |
| Nature genetics. 1997 ; 17 (4) : 467-470. |
| PMID 9398852 |
| |
| A non-AUG translational initiation event generates novel WT1 isoforms. |
| Bruening W, Pelletier J |
| The Journal of biological chemistry. 1996 ; 271 (15) : 8646-8654. |
| PMID 8621495 |
| |
| Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms' tumor locus. |
| Call KM, Glaser T, Ito CY, Buckler AJ, Pelletier J, Haber DA, Rose EA, Kral A, Yeger H, Lewis WH |
| Cell. 1990 ; 60 (3) : 509-520. |
| PMID 2154335 |
| |
| Characterization of the genomic breakpoint and chimeric transcripts in the EWS-WT1 gene fusion of desmoplastic small round cell tumor. |
| Gerald WL, Rosai J, Ladanyi M |
| Proceedings of the National Academy of Sciences of the United States of America. 1995 ; 92 (4) : 1028-1032. |
| PMID 7862627 |
| |
| Infrequent mutation of the WT1 gene in 77 Wilms' Tumors. |
| Gessler M, König A, Arden K, Grundy P, Orkin S, Sallan S, Peters C, Ruyle S, Mandell J, Li F |
| Human mutation. 1994 ; 3 (3) : 212-222. |
| PMID 8019557 |
| |
| Homozygous deletion in Wilms tumours of a zinc-finger gene identified by chromosome jumping. |
| Gessler M, Poustka A, Cavenee W, Neve RL, Orkin SH, Bruns GA |
| Nature. 1990 ; 343 (6260) : 774-778. |
| PMID 2154702 |
| |
| Alternative splicing and genomic structure of the Wilms tumor gene WT1. |
| Haber DA, Sohn RL, Buckler AJ, Pelletier J, Call KM, Housman DE |
| Proceedings of the National Academy of Sciences of the United States of America. 1991 ; 88 (21) : 9618-9622. |
| PMID 1658787 |
| |
| Frasier syndrome is caused by defective alternative splicing of WT1 leading to an altered ratio of WT1 +/-KTS splice isoforms. |
| Klamt B, Koziell A, Poulat F, Wieacker P, Scambler P, Berta P, Gessler M |
| Human molecular genetics. 1998 ; 7 (4) : 709-714. |
| PMID 9499425 |
| |
| Subnuclear localization of WT1 in splicing or transcription factor domains is regulated by alternative splicing. |
| Larsson SH, Charlieu JP, Miyagawa K, Engelkamp D, Rassoulzadegan M, Ross A, Cuzin F, van Heyningen V, Hastie ND |
| Cell. 1995 ; 81 (3) : 391-401. |
| PMID 7736591 |
| |
| A clinical overview of WT1 gene mutations. |
| Little M, Wells C |
| Human mutation. 1997 ; 9 (3) : 209-225. |
| PMID 9090524 |
| |
| Germline mutations in the Wilms' tumor suppressor gene are associated with abnormal urogenital development in Denys-Drash syndrome. |
| Pelletier J, Bruening W, Kashtan CE, Mauer SM, Manivel JC, Striegel JE, Houghton DC, Junien C, Habib R, Fouser L |
| Cell. 1991 ; 67 (2) : 437-447. |
| PMID 1655284 |
| |
| Binding of the Wilms' tumor locus zinc finger protein to the EGR-1 consensus sequence. |
| Rauscher FJ 3rd, Morris JF, Tournay OE, Cook DM, Curran T |
| Science (New York, N.Y.). 1990 ; 250 (4985) : 1259-1262. |
| PMID 2244209 |
| |
| Internal translation initiation generates novel WT1 protein isoforms with distinct biological properties. |
| Scharnhorst V, Dekker P, van der Eb AJ, Jochemsen AG |
| The Journal of biological chemistry. 1999 ; 274 (33) : 23456-23462. |
| PMID 10438524 |
| |
| Fine structure analysis of the WT1 gene in sporadic Wilms tumors. |
| Varanasi R, Bardeesy N, Ghahremani M, Petruzzi MJ, Nowak N, Adam MA, Grundy P, Shows TB, Pelletier J |
| Proceedings of the National Academy of Sciences of the United States of America. 1994 ; 91 (9) : 3554-3558. |
| PMID 8170946 |
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