TY - JOUR
T1 - Confirmation of FWT1 as a Wilms' tumour susceptibility gene and phenotypic characteristics of Wilms' tumour attributable to FWT1
AU - Rahman, Nazneen
AU - Abidi, Fatima
AU - Ford, Deborah
AU - Arbour, Laura
AU - Rapley, Elizabeth
AU - Tonin, Patricia
AU - Barton, David
AU - Batcup, Gillian
AU - Berry, Jem
AU - Cotter, Finbarr
AU - Davison, Val
AU - Gerrard, Mary
AU - Gray, Elizabeth
AU - Grundy, Richard
AU - Hanafy, Magdi
AU - King, Derek
AU - Lewis, Ian
AU - Luethy, Annette Ridolfi
AU - Madlensky, Lisa
AU - Mann, Jill
AU - O'Meara, Anne
AU - Oakhill, Tony
AU - Skolnick, Mark
AU - Strong, Louise
AU - Variend, Dick
AU - Narod, Steven
AU - Schwartz, Charles
AU - Pritchard-Jones, Kathryn
AU - Stratton, Michael R.
N1 - Funding Information:
Acknowledgements The authors thank the families for their cooperation. We thank Drs. S. Hasstedt, T. McClellan, T. Bishop and B. Hane for their assistance with the work on K1104, and J. Pritchard and F. Raafat. The WT families in Britain were identified by Charles Stiller and specimens were collected with the help of the UK Children’s Cancer Study Group. The incidence data on WT in Great Britain were provided by the National Registry of Childhood tumours at the Childhood Cancer Research Group. The work was supported by the Medical Research Council (UK), the Cancer Research Campaign, the South Carolina Department of Disabilities and Special Needs, the Canadian Genetic Diseases Network, the Canadian Breast Cancer Foundation and the Fonds de la Recherche en Sante du Quebec. The experiments comply with the current laws of Great Britain.
PY - 1998
Y1 - 1998
N2 - A susceptibility gene for Wilms' tumour (WT), designated FWT1, was previously mapped to chromosome 17q12-q21 by linkage analysis of a single family. We now confirm the existence of this gene by analysis of additional cases in the original family (3-point LOD score = 5.69), and by detecting strong evidence of linkage to this region in an unrelated pedigree with seven cases of WT (3-point LOD score = 2.56). Analysis of 11 smaller WT families confirms that there is genetic heterogeneity in familial WT, as three families exhibit strong evidence against linkage to FWT1. One of these was subsequently found to have a predisposing WT1 mutation. However, the other two families show evidence against both FWT1 and WT1, suggesting that at least one further familial WT gene exists. Analysis of the phenotype of 16 WT cases from the families linked to FWT1 demonstrates that they present at a significantly older age and a significantly later stage than both sporadic WT and the six cases from two families unlinked to either FWT1 or WT1. The results confirm the role of FWT1 in susceptibility to WT, provide strong evidence for genetic heterogeneity in familial WT and suggest there are phenotypic differences between familial WT due to FWT1, familial WT due to other genes and non-familial WT.
AB - A susceptibility gene for Wilms' tumour (WT), designated FWT1, was previously mapped to chromosome 17q12-q21 by linkage analysis of a single family. We now confirm the existence of this gene by analysis of additional cases in the original family (3-point LOD score = 5.69), and by detecting strong evidence of linkage to this region in an unrelated pedigree with seven cases of WT (3-point LOD score = 2.56). Analysis of 11 smaller WT families confirms that there is genetic heterogeneity in familial WT, as three families exhibit strong evidence against linkage to FWT1. One of these was subsequently found to have a predisposing WT1 mutation. However, the other two families show evidence against both FWT1 and WT1, suggesting that at least one further familial WT gene exists. Analysis of the phenotype of 16 WT cases from the families linked to FWT1 demonstrates that they present at a significantly older age and a significantly later stage than both sporadic WT and the six cases from two families unlinked to either FWT1 or WT1. The results confirm the role of FWT1 in susceptibility to WT, provide strong evidence for genetic heterogeneity in familial WT and suggest there are phenotypic differences between familial WT due to FWT1, familial WT due to other genes and non-familial WT.
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U2 - 10.1007/PL00008708
DO - 10.1007/PL00008708
M3 - Article
C2 - 9860296
AN - SCOPUS:0031736957
SN - 0340-6717
VL - 103
SP - 547
EP - 556
JO - Human genetics
JF - Human genetics
IS - 5
ER -