Hereditary cancer and developmental abnormalities.
About 1% of all cancers are hereditary, caused by germ-line mutations in specific cancer-related genes. More than 25 different hereditary cancer syndromes are known, most of them involving mutations in tumor suppressor genes. These genes, which are related to cellular proliferation, might also be involved in differentiation. Hence, the phenotype of hereditary cancer syndromes might include developmental abnormalities, in addition to cancer predisposition. The information summarized here indicates that developmental phenotypes appear in both human patients and mouse models of the various hereditary cancer syndromes. These developmental abnormalities, which involve a variety of tissues and organs, usually lead to embryonic malformation that prevents the birth of viable homozygous offspring, but can also be detected in heterozygotes. In some of the syndromes a correlation exists between tumor types and developmentally affected tissues. Comparison of mice and human phenotypes from both the cancer and the developmental aspects indicates that many of the mouse models mimic the human syndromes. Our analysis indicates that most tumor suppressor genes participate not only in the regulation of cell proliferation, but also in differentiation and embryogenesis.
Ben-Yosef
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Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Benvenisty
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D000818:Animals; D000013:Congenital Abnormalities / Q000235:genetics*; D004195:Disease Models, Animal; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D005808:Genes, Recessive / Q000235:genetics; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D009369:Neoplasms / Q000235:genetics*; D010641:Phenotype