TY - CHAP

T1 - Origin of testicular germ cell neoplasia

T2 - The role of sex chromosomes

AU - Rajpert-De Meyts, Ewa

AU - Ottesen, Anne Marie

AU - Hoei-Hansen, Christina

AU - Sonne, Si Brask

AU - Leffers, Henrik

AU - Skakkebæk, Niels E.

N1 - Publisher Copyright: © 2007 by World Scientific Publishing Co. Pte. Ltd. All rights reserved.

PY - 2007/1/1

Y1 - 2007/1/1

N2 - Germ cell neoplasms, a cancer type most common in young individuals, are found mainly in the gonads. Testicular tumors in adolescents and young adults are derived from a preinvasive precursor cell called carcinoma in situ (CIS) or intratubular germ cell neoplasia, unclassified (ITGCNU). CIS has features of immature fetal germ cells, and is believed to originate from developmentally arrested primordial germ cells or gonocytes. In most cases, the arrest is caused by gonadal dysgenesis, a multifactorial and complex syndrome that has a broad spectrum of phenotypes, ranging from moderate impairment of spermatogenesis to a variety of intersex disorders. Testicular dysgenesis syndrome may be a result of inherited genetic aberrations, but in most cases the pathogenesis is unknown, although it is suspected that genes involved in sex differentiation go through transcriptional or functional deregulation caused by external environmental factors. The effects of these factors are likely modulated by genomic variations (polymorphisms), thus explaining the individual- and population-level differences. In this article, the existing evidence concerning the role of the sex chromosomes is reviewed, with emphasis on aneuploidy and structural aberrations, which carry a high risk of germ cell neoplasia. Less is known about the role of single genes or gene polymorphisms in germ cell development and neoplastic transformation. We hypothesize that factors disturbing gonadal development (including imbalance between the Y and X chromosomes) may lead to impaired germ cell differentiation and prolonged expression of pluripotency genes, and may increase the risk of neoplastic transformation of germ cells.

AB - Germ cell neoplasms, a cancer type most common in young individuals, are found mainly in the gonads. Testicular tumors in adolescents and young adults are derived from a preinvasive precursor cell called carcinoma in situ (CIS) or intratubular germ cell neoplasia, unclassified (ITGCNU). CIS has features of immature fetal germ cells, and is believed to originate from developmentally arrested primordial germ cells or gonocytes. In most cases, the arrest is caused by gonadal dysgenesis, a multifactorial and complex syndrome that has a broad spectrum of phenotypes, ranging from moderate impairment of spermatogenesis to a variety of intersex disorders. Testicular dysgenesis syndrome may be a result of inherited genetic aberrations, but in most cases the pathogenesis is unknown, although it is suspected that genes involved in sex differentiation go through transcriptional or functional deregulation caused by external environmental factors. The effects of these factors are likely modulated by genomic variations (polymorphisms), thus explaining the individual- and population-level differences. In this article, the existing evidence concerning the role of the sex chromosomes is reviewed, with emphasis on aneuploidy and structural aberrations, which carry a high risk of germ cell neoplasia. Less is known about the role of single genes or gene polymorphisms in germ cell development and neoplastic transformation. We hypothesize that factors disturbing gonadal development (including imbalance between the Y and X chromosomes) may lead to impaired germ cell differentiation and prolonged expression of pluripotency genes, and may increase the risk of neoplastic transformation of germ cells.

KW - Carcinoma in situ testis

KW - Dysgenesis

KW - Germ cell tumor

KW - Testicular

KW - Testicular neoplasms

KW - X chromosome

KW - Y chromosome

UR - http://www.scopus.com/inward/record.url?scp=40349107308&partnerID=8YFLogxK

U2 - 10.1142/9789812770431_0014

DO - 10.1142/9789812770431_0014

M3 - Book chapter

AN - SCOPUS:40349107308

SN - 9812703748

SN - 9789812703743

SP - 289

EP - 308

BT - The Y Chromosome and Male Germ Cell Biology in Health and Diseases

PB - World Scientific Publishing Co.

ER -