Chromosomes, genes, and development of testicular germ cell tumors

A literature review found 265 articles on testicular germ cell tumors (TGCTs) detailing the copy number of chromosomal regions and expression of 245 genes. An initial precursor stage, intratubular germ cell neoplasia (IGCN), is characterized by triploidization and an upregulation of KIT, ALPP, CCDN2, and ZNF354A, and a downregulation of CDKN2D. TGCT regularly have a series of chromosomal aberrations: a decrease in copy number at 4q21similar toqter and 5q14similar toqter; an increase at 7p21similar topter, 7q21similar toq33, and 8q12similar toq23 (especially high increase in seminoma); a decrease at 11p11similar top15 and 11q14similar toq24; an increase at 12p11similar topter; a decrease at 13q14similar toq31; an increase of 17q11similar toq21 (only for nonseminoma); a decrease of 18q12similar toqter; and an increase at 21q21similar toqter, 22q11similar toqter (only for seminoma), and Xq. Macroscopically overt TGCT is associated with a characteristic series of abnormalities in the retinoblastoma pathway including upregulation of cyclin D2 and p27 and downregulation of RB1 and the cyclin-dependent kinase inhibitors p16, p18, p19, and p21. TGCT thus has a synergistic pattern in gene expressions of the retinoblastoma pathway that is rare in other malignancies. (C) 2004 Elsevier Inc. All rights reserved.