ABSTRACT
A tumor arises because of a deregulated proliferation of cells that forms an abnormal mass. Tumorigenesis is a multistep process in which normal controls of cell proliferation and cell-cell interaction are lost. In the human genome, there are various types of genes that control cell growth through very precise mechanisms. Tumorigenesis involves interplay between at least two classes of genes: (1) oncogenes and (2) tumor suppressor genes. Alterations in any one or both of these classes of genes and their pathways could lead to tumor formation. Human primary brain tumors are a diverse group of neoplasms arising from different cells of the central nervous system. The vestibular
11.1 Introduction to Human Cancers ........................................................................................... 214 11.1.1 Human Tumor Suppressor Genes ............................................................................. 214 11.1.2 The Human Retinoblastoma Gene ........................................................................... 215
11.2 Epidemiology: Prevalence .................................................................................................... 217 11.2.1 Human Vestibular Schwannomas ............................................................................. 217 11.2.2 Patient Information ................................................................................................... 219 11.2.3 Loss of Heterozygosity at the RB1 Gene Locus in Human VS Tumors ................... 219 11.2.4 RB1 Gene Expression in VS Tumors ........................................................................220 11.2.5 Level and Phosphorylation Status of pRb in VS Tumors ......................................... 221
11.3 Hypothesis ............................................................................................................................ 222 11.4 Conclusion ............................................................................................................................ 222 Internet Resources .......................................................................................................................... 223 References ...................................................................................................................................... 223
schwannomas (VS) arise from the vestibular branch of the eighth cranial nerve, the vestibulocochlear nerve. Despite marked improvement in diagnosis, management, and treatment protocols, these tumors continue to cause signišcant morbidity. If the VS tumor becomes large, it can exert pressure on other cranial nerves, interfere with their functions, and eventually cause mortality. In addition to tumors arising from the vestibulocochlear nerve, patients with VS tumors also develop other secondary malignant tumors such as meningiomas, gliomas, and spinal schwannomas. The RB1 gene is the šrst human tumor suppressor gene to be identišed. Genetic alterations at the RB1 gene locus have been reported in human retinoblastomas, which is a human childhood tumor. RB1 gene alterations have also been reported in other human tumors such as osteosarcoma and softtissue sarcoma and cancers of lung, breast, and bladder. The protein product of this gene, pRb, is known to be involved in cell cycle regulation. The functions of pRb are modulated by its phosphorylation and dephosphorylation. There are 16 phosphorable Ser/Thr sites in pRb. Deregulation of phosphorylation or dephosphorylation of pRb is known to affect its function as a tumor suppressor. In this chapter, we will discuss the possible role of the RB1 gene and its protein product in human VS tumors.
