Loss of heterozygosity in somatic cells of the mouse. An important step in cancer initiation?
Loss of heterozygosity (LOH) of tumour suppressor genes is a crucial step in the development of sporadic and hereditary cancer. Recently, we and others have developed mouse models in which the frequency and nature of LOH events at an autosomal locus can be elucidated in genetically stable normal somatic cells. In this paper, an overview is presented of recent studies in LOH-detecting mouse models. Molecular mechanisms that lead to LOH and the effects of genetic and environmental variables are discussed. The general finding that LOH of a marker gene occurs frequently in somatic cells of the mouse without deleterious effects on cell viability, suggests that also tumour suppressor genes are lost in similar frequencies. LOH of tumour suppressor genes may thus be an initiating event in cancer development.
Wijnhoven
S W
SW
Department of Radiation Genetics and Chemical Mutagenesis-MGC, Leiden University Medical Center, P.O. Box 9503, 2333 AL, Leiden, The Netherlands.
Kool
H J
HJ
van Teijlingen
C M
CM
van Zeeland
A A
AA
Vrieling
H
H
D000818:Animals; D002273:Carcinogens / Q000494:pharmacology; D006801:Humans; D019656:Loss of Heterozygosity / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D051379:Mice; D023421:Models, Animal; D009369:Neoplasms / Q000209:etiology* / Q000235:genetics
D002273:Carcinogens