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

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