title: Aneuploidy of human testicular germ cell tumors is associated with amplification of centrosomes.
abstract: Testicular germ cell tumors occur in three age groups. Seminomas and nonseminomas of adults, including mature teratomas, and the precursor carcinoma in situ (CIS) are aneuploid. This also holds true for yolk sac tumors of newborn and infants, while the mature teratomas of this age are diploid. In contrast, spermatocytic seminomas occurring in the elderly contain both diploid and polyploid cells. Aneuploidy has been associated with centrosome aberrations, sometimes related to overexpression of STK15. Aneuploidy of non-neoplastic germ cells has been demonstrated in the context of male infertility, a risk factor for the development of seminoma/nonseminoma. We investigated aneuploidy, centrosome aberrations and the role of STK15 in different types of testicular germ cell tumors as well as in normal and disturbed spermatogenesis. The aneuploid seminomas and nonseminomas tumors (including CIS) showed increased numbers of centrosomes, without STK15 amplification or overexpression. Four out of six infantile teratomas had normal centrosomes, the remaining two and an infantile yolk sac tumor showed a heterogeneous pattern of cells with normal or amplified centrosomes. Spermatocytic seminomas had two, four or eight centrosomes. Germ cells in seminiferous tubules with disturbed spermatogenesis shared both aneuploidy and centrosome abnormalities with seminomas/nonseminomas and showed a more intense STK15 staining than those with normal spermatogenesis and CIS. Therefore, aneuploidy of testicular germ cell tumors is associated with amplified centrosomes probably unrelated to STK15.
authors.affiliation: Pathology/Laboratory for Experimental Patho-Oncology, Josephine Nefkens Institute, Erasmus Medical Center/Daniel den Hoed Cancer Center, 3000 DR Rotterdam, The Netherlands.
authors.forename: Frank
authors.initials: F
authors.lastname: Mayer
authors.forename: Hans
authors.initials: H
authors.lastname: Stoop
authors.forename: Subrata
authors.initials: S
authors.lastname: Sen
authors.forename: Carsten
authors.initials: C
authors.lastname: Bokemeyer
authors.forename: J Wolter
authors.initials: JW
authors.lastname: Oosterhuis
authors.forename: Leendert H J
authors.initials: LH
authors.lastname: Looijenga
mesh_terms: D000293:Adolescent; D000328:Adult; D000782:Aneuploidy; D001284:Atrophy; D064096:Aurora Kinase A; D064127:Aurora Kinases; D018236:Carcinoma, Embryonal / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D018385:Centrosome / Q000648:ultrastructure*; D002877:Chromosomes, Human / Q000648:ultrastructure*; D018240:Endodermal Sinus Tumor / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D005784:Gene Amplification; D018237:Germinoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007984:Leydig Cell Tumor / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D012671:Seminiferous Tubules / Q000201:enzymology / Q000473:pathology; D018239:Seminoma / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D013091:Spermatogenesis; D013724:Teratoma / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D013736:Testicular Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D013737:Testis / Q000473:pathology
chemical_list: D009363:Neoplasm Proteins; C576917:AURKA protein, human; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases