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 4q21∼qter and 5q14∼qter; an increase at 7p21∼pter, 7q21∼q33, and 8q12∼q23 (especially high increase in seminoma); a decrease at 11p11∼p15 and 11q14∼q24; an increase at 12p11∼pter; a decrease at 13q14∼q31; an increase of 17q11∼q21 (only for nonseminoma); a decrease of 18q12∼qter; and an increase at 21q21∼qter, 22q11∼qter (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.