Gene: [11p13/WT1] Wilms tumor suppressor 1; Wilms tumor 1 (nephroblastoma; mesothelioma?); WAGR syndrome (MIM:194072); Denys-Drash syndrome (MIM:194080); [WAGR WTCR1 ]
|
GEN |
The gene length: 50 kbp; exons: 10 (Haber-1991). |
|
FUN |
The WT1 protein isoforms have several characteristics of zinc-finger transcription factors and are thought to regulate gene expression during mesenchymal to epithelial cell differentiation (Pritchard-Jones-1990) especially in the development of the urogenital system." |
|
PAT |
Wilms tumor (WT) is one of the most common solid tumors of childhood, occurring in 1 in 10,000 children and accounting for 8% of childhood cancers. It is believed to result from malignant transformation of abnormally persistent renal stem cells which retain embryonic differentiation potential (Breslow-1982)." |
|
MUT |
By PCR-SSCP analysis of 98 sporadic Wilms tumors, Varanasi-1994 found that mutations in the WT1 gene are rare, occurring in only 6 tumors analyzed. In 1 sample, 2 independent intragenic mutations inactivated both WT1 alleles, providing a singular example of 2 different somatic alterations restricted to the WT1 gene. The data, together with the previously ascertained occurrence of large deletions/insertions in WT1, defined the frequency at which the WT1 gene is altered in sporadic tumors." |
|
HET |
[1] This locus was previously assumed to be related with the combined
syndrome WAGR, which included, in addition to Wilms tumor, aniridia,
gonadoblastoma, and mental retardation (AGR triade; Riccardi-1978).
Many authors found WAGR to be accompanied by deletions in the chr 11
short arm, so WAGR locus was considered as being located in segment
11p13. However, aniridia and genital abnormalities were later
demonstrated to occur independently of both Wilms tumor and each
other. Therefore, the WAGR locus was excluded from gene catalogues and
replaced by three independent genes - GEM:11p13/WT1, GEM:11p13/PAX6,
and GEM:11p13/GUD.
[2] The MTACR1 locus related to Wilms tumor (WT2#) is supposed to be located in chr 11 (GEM:11p155/MTACR1). It was also demonstrated that one of the Wilms tumor types is not linked to chr 11; the MIM and HUGEN registered this locus as WT3 (GEM:00.0/WT3) and GDB, as WT2. Several other genes or chromosomal areas had been associated with the development of Wilms tumor: GEM:17q/WT4; GEM:07p1/WT7." |
|
REF |
LOC,CYG,PAT "Anderson SR &: Ophthalmologica, 176, 171-177, 1978 REV,PAT,FOG "Babajan RJ &: Cancer, 45, 1713-1719, 1980 LIN,MOL "Bonetta L &: CCG, 51, (HGM10), 965, 1989 PAT,POG "Breslow NE, Beckwith JR: J Nat Cancer Inst, 68, 429-436, 1982 MAP,MGC "Davis LM &: Science, 241, (12 Aug), 840-842, 1988 HIS,PAT,PHE "DiGeorge AM, Harley RDL: Arch Ophthal, 75, 796-798, 1966 MUT,MOP,EXP "Englert C &: PNAS, 92, 11960-11964, 1995 HIS,PAT,PHE "Fitzgerald WL, Hardin HC: J Urol, 73, 468-474, 1955 GEN,MUT,POG "Gerald WL &: PNAS, 92, 1028-1032, 1995 GEN,SEQ,EXP "Gessler M &: Genomics, 17, 499-501, 1993 GEN,SEQ,EXP "Gessler M &: Genomics, 12, 807-813, 1992 PRO,LOC,LIN "Gessler M &: Genomics, 5, 43-55, 1989a PRO,LOC,LIN "Gessler M, Bruns GAP: CCG, 51, (HGM10), 1003-1004, 1989b LOC,MOL,LIN,ENG "Glaser T &: Genomics, 6, N1, 48-64, 1990 PRO,LOC,MAP,POL "Glaser T &: CCG, 51, (HGM10), 1005, 1989 PAT,MUT "Grubb GR &: Oncogene, 10, 1677-1681, 1995 MUT,PAT "Haber DA &: PNAS, 89, 6010-6014, 1992 GEN,MUT,PAT "Haber DA &: PNAS, 88, 9618-9622, 1991 MUT,PAT "Hastie ND: Hum Mol Genet, 1, 293-295, 1992 LIN,MOL,FAG "Henry I &: PNAS, 86, 3247-3251, 1989 LIN,MOL,FAG "Henry I &: CCG, 46, (HGM9), 628-629, 1987a LIN,MOL,FAG "Henry I &: CCG, 46, (HGM9), 629, 1987b PAT,MUT "Huff V &: AJHG, 56, 84-90, 1995 PAT,MUT "Kikuchi H &: FEBS Lett, 360, 26-28, 1995 REV,PAT,FOG "Knudson, Strong: AJHG, 27, 809-810, 1972 REV,PAT,FOG "Kolata GB: Science, 207, 970-971, 1980 LOC,MAP "Lewis WH &: Genomics, 3, N1, 25-31, 1988 LIN,MAP,MOL "Mannens M &: Hum Genet, 81, 41-48, 1988 MOP,FUN,EXP "Pritchard-Jones K &: Nature, 346, 194-197, 1990 LOC,CYG,PAT "Riccardi VM &: Pediatrics, 61, 604-610, 1978 LIN,MAF "Rose EA &: Cell, 60, 405-508, 1990 HIS,PAT,PHE "Strom T: Acta Paediatr, 46, 601-604, 1957 LOC,MAP "van Heyningen V &: CCG, 46, (HGM9), 708, 1987 LOC,MAP "van Heyningen V &: PNAS, 82, N24, 8592-8596, 1985 GEN,MUT,POG "Varanasi R &: PNAS, 91, 3554-3558, 1994 LIN,MOL,FAG "Wadey &: CCG, 51, (HGM10), 1100, 1989 |
|
KEY |
onc, ren |
|
CLA |
coding, basic |
|
LOC |
11 p13 |
|
MIM |
MIM: 194070 |
|
SYN |
WAGR WTCR1 |
