The cytogenetic theory of the pathogenesis of human adult male germ cell tumors. Review article

APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica
R S Chaganti, J Houldsworth

Abstract

Human male germ cell tumors (GCTs) represent a biological paradox because, in order to develop into a pluripotential tumor, a germ cell destined to a path of limited or no proliferation must acquire the potential for unlimited proliferation. In addition, it must acquire the ability to elicit embryonal differentiation patterns without the reciprocal inputs from fertilization and the imprinting-associated genomic changes which are a part of normal embryonal development. Although much speculated about, the genetic mechanisms underlying these properties of male GCTs remain enigmatic. Recent cytogenetic and molecular genetic analyses of these tumors are providing new insights and new testable hypotheses. Based on our recent work, we propose two such hypotheses. One relates to the mechanism of germ cell transformation and germ cell tumor development. We suggest that the invariable 12p amplification noted as early as in carcinoma in situ/intratubular germ cell neoplasia (CIS/ITGCN) lesions leads to deregulated overexpression of cyclin D2, a cell cycle G1/S checkpoint regulator with oncogeneic potential. Such overexpression reinitiates the cell cycle. We visualize this happening during the pachytene stage of meiosis through aberrant re...Continue Reading

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