Aneuploidy of human testicular germ cell tumors is associated with amplification of centrosomes

Frank Mayer, Hans Stoop, Subrata Sen, Carsten Bokemeyer, J Wolter Oosterhuis, Leendert H J Looijenga

Research output: Contribution to journalArticlepeer-review

53 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3859-66
Number of pages8
JournalOncogene
Volume22
Issue number25
DOIs
Publication statusPublished - 19 Jun 2003
Externally publishedYes

Keywords

  • Adolescent
  • Adult
  • Aneuploidy
  • Atrophy
  • Aurora Kinase A
  • Aurora Kinases
  • Carcinoma, Embryonal/enzymology
  • Centrosome/ultrastructure
  • Chromosomes, Human/ultrastructure
  • Endodermal Sinus Tumor/enzymology
  • Gene Amplification
  • Germinoma/enzymology
  • Humans
  • Infant
  • Infant, Newborn
  • Leydig Cell Tumor/enzymology
  • Lymphoma, B-Cell/enzymology
  • Male
  • Middle Aged
  • Neoplasm Proteins/genetics
  • Protein Serine-Threonine Kinases/genetics
  • Seminiferous Tubules/enzymology
  • Seminoma/enzymology
  • Spermatogenesis
  • Teratoma/enzymology
  • Testicular Neoplasms/enzymology
  • Testis/pathology

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