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Incipient Events in Human Carcinogenesis: A Concept of Forerunner Genes

  • Bogdan Czerniak
Chapter
Part of the TTME book series (TTME, volume 2)

Abstract

Many common epithelial human cancers start as in situ expansions of cells, which exhibit almost normal phenotype. Such expansions form large plaques involving the affected mucosal membrane and are antecedent to the development of dysplasia or carcinoma in situ. Here we describe a whole-organ genomic mapping strategy to identify specific chromosomal regions involved in the development of early intraurothelial lesions in human bladder carcinogenesis. High resolution mapping of one such regions containing the model tumor suppressor RB1 provided evidence supporting the existence of a new class of genes termed forerunner (FR) genes. These genes map near tumor suppressors and provide a critical driving force for the early clonal expansion of neoplastic cells. The FR genes are related to tumor suppressors as they contribute to tumor development by their loss of function but their inactivation occurs prior to that of tumor suppressors such as RB1 in tumorigenesis.

Keywords

Bladder cancer Carcinogenesis Whole-organ genetic mapping Forerunner genes Hyperplasia In situ neoplasia Loss of heterozygosity (LOH) Polymorphism Genetic instability Homologous recombination 

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Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • Bogdan Czerniak
    • 1
  1. 1.Department of Pathology, Nathan W. Lassiter Distinguished Chair in Urology, Department of PathologyThe University of Texas, MD Anderson Cancer CenterHoustonUSA

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