TY - JOUR
T1 - A developmental context for multiple genetic alterations in Wilms' tumor
AU - Feinberg, A. P.
PY - 1994
Y1 - 1994
N2 - Wilms' tumor has served as an example of Knudson's two-hit hypothesis of recessive tumor genes, but the genetics has proven to be surprisingly complex. WT1, a tumor suppressor gene on 11p13, is mutated in only a small fraction of Wilms' tumors, and a second chromosomal region, 11p15, harbors a second Wilms' tumor gene also involved in other cancers. In addition, loss of genomic imprinting, or parental origin-specific gene expression of at least two genes, appears to be an early step in Wilms' tumorigenesis and common cancers. Finally, genes on other chromosomes also play a role. I propose a model of Wilms' tumorigenesis in which multiple genetic alterations act within a specific developmental context, accounting for the epidemiological and pathological heterogeneity of Wilms' tumor, as well as the tissue specificity of the tumor types arising from alterations in these genes.
AB - Wilms' tumor has served as an example of Knudson's two-hit hypothesis of recessive tumor genes, but the genetics has proven to be surprisingly complex. WT1, a tumor suppressor gene on 11p13, is mutated in only a small fraction of Wilms' tumors, and a second chromosomal region, 11p15, harbors a second Wilms' tumor gene also involved in other cancers. In addition, loss of genomic imprinting, or parental origin-specific gene expression of at least two genes, appears to be an early step in Wilms' tumorigenesis and common cancers. Finally, genes on other chromosomes also play a role. I propose a model of Wilms' tumorigenesis in which multiple genetic alterations act within a specific developmental context, accounting for the epidemiological and pathological heterogeneity of Wilms' tumor, as well as the tissue specificity of the tumor types arising from alterations in these genes.
KW - 11p15 tumor suppressor gene
KW - Genomic imprinting
KW - H19
KW - IGF2
KW - WT1
KW - Wilms' tumor
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U2 - 10.1242/jcs.1994.supplement_18.2
DO - 10.1242/jcs.1994.supplement_18.2
M3 - Review article
C2 - 7883796
AN - SCOPUS:0028706337
SN - 0021-9533
VL - 107
SP - 7
EP - 12
JO - Journal of cell science
JF - Journal of cell science
IS - SUPPL. 18
ER -