Tumor suppressor gene Table

TABLE 5.22 Important Oncogenes and Tumor Suppressor Genes in Human Cancers... 

TABLE 85-1. Examples of Oncogenes and Tumor-Suppressor Genes... 

A selection of other tumor suppressor genes is summarized in Table 14.2. Interestingly, an enzyme of phosphatidyl-inositol metabolism has been also identified as a tumor suppressor. The PTEN tumor suppressor gene codes for a phospholipid phosphatase which specifically cleaves a phosphate from the second messenger phosphatidyl-inosi-tol-3,4,5-trisphosphate (PtdInsPj, see 6.6.2). and thus inactivates the messenger (review Maehama and Dixon, 1999). ... 

A number of tumor suppressor genes are known with no direct relationship to the regulation of the cell cycle. Some of the tumor suppressor genes in Table 14.2 are involved in the organization of the cytoskeleton or in cell-cell interactions. 

The data accumulated for trout clearly indicates that both the type of inducing compound and the tissue investigated affect the ras mutational spectrum and incidence observed (Table 2). Furthermore, these extensive studies using trout also show that the ras mutational profile differs from that observed in rodent models. There are no reports as yet of p53, or any other tumor suppressor gene, mutations in trout tumor tissue despite readily available methods". While an apparent lack of similarity in mutational profiles may exclude trout as a viable model of mammalian carcinogenesis at the molecular mechanistic level, there still remains the enormous potential by virtue of their induced triploidy status in the development of trout as a model of heritable disease where tumor suppressor genes are implicated. 

Whereas oncogenes are characterized by gain of function, another class of genes are characterized by loss of function these are the tumor suppressor genes, which are often involved in familial (inherited) cancers (Table 26-7). The rare human cancer retinoblastoma provided the first significant insight into tumor suppressor genes. Retinoblastoma affects about 1 in 20,000 children who usually develop tumors in both eyes. Affected individuals have a small deletion in chromosome 13 that... 

Many human genes produce proteins called tumor suppressors. Tumor suppressors inhibit transcription of genes that would cause increased replication. When a mutation occurs in any of these suppressors, replication and division become uncontrolled and tumors result. Table 14.3 lists some human tumor-suppressor genes. 

Oncogenes and tumor suppressor genes that have been linked to specific types of cancer are identified in Table 42.1. Table 42.2 relates oncogenic markers of selected cancers to disease prognosis and treatment strategy. 

Figure 50. PTEN. The tumor suppressor gene and gene product protein PTEN (phosphatase tensin homolog deleted on chromosome ten, human 10q23.3) (Table VIII), is the natural inhibitor of oncogenes PI3K/Akt (phosphatidyl inositol kinase 3 protein kinase 3 phosphatidylinositol 3 phosphate Jacob Furth s AK mouse strain thymic lymphoma retroviral oncogene phosphoinosite-dependent kinase). The PTEN protein inactivates PIP3 by dephosphorylation PDKl (phosphoinositol-dependent kinase) is not recruited to the plasma membrane to activate Akt by phosphorylation. Sarah M. Planchon et al. The nuclear affairs of PTEN. J Cell Sci 2008 121 249-253. doi 10.1242/jcs.022459...

Since the pioneering work by Knudson in the early 1970s, a correlation between mutated tumor suppressor genes and different cancers has been found in several cases, such as BRCAl (cancers of breast, ovary, colon and prostate), BRCA2 (cancers of breast, ovary, pancreas and prostate), CDK4 (melanoma) and PMSl and PMS2 (colorectal cancer), just to mention a few. Representative tumor suppressor genes, their functions and the pathways affected are listed in Table 1.3. 

Renal tumors can occur as part of complex genetic diseases (Table 3.7). Tumors are major manifestations in the two forms of tuberous sclerosis and the von Hippel-Lindau syndrome. The responsible genes are tumor suppressor genes. The two step hypothesis of Knudson gives an explanation for the great clinical variability. 

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