Why human extragonadal germ cell tumours occur in the midline of the body: old concepts, new perspectives.
Hypotheses on the origin and distribution of extragonadal germ cell tumours (GCTs) and teratomas are briefly reviewed and revisited in the light of (i) new developments in the classification of GCTs, (ii) data on genomic imprinting of these neoplasms and (iii) the recent finding that germ cells can be derived from mouse and human embryonal stem (ES) cells. Only the Type I (infantile teratomas/yolk sac tumours) and Type II GCTs (seminomatous tumours and non-seminomas) occur in the gonads and extragonadal localizations. The data on genomic imprinting lend support to the hypothesis that they are derived from germ cells. These precursor cells could have differentiated from ES cells in extragonadal localizations. Their distribution along the midline of the body is still best explained by the migration of primitive germ cells during development. The narrower distribution of the Type II than the Type I GCTs is probably due to the more strict conditions for survival and proliferation of primordial germ cells (PGCs)/gonocytes from which the Type II tumours originate, when compared with the precursor cells of Type I tumours, probably primitive germ cells closer to the ES cell. The known niches in which the Type II tumours develop have in common that they contain feeder cells expressing stem cell factor (SCF) - the ligand for the SCF receptor c-KIT, involved in proliferation and survival of PGCs/gonocytes - and contain GBY including the gene TSPY.
Oosterhuis
J Wolter
JW
Department of Pathology, Erasmus University Medical Center, Josephine Nefkens Institute, Rotterdam, The Netherlands. j.w.oosterhuis@erasmusmc.nl
Stoop
Hans
H
Honecker
Friedemann
F
Looijenga
Leendert H J
LH
D000818:Animals; D053595:Embryonic Stem Cells / Q000473:pathology / Q000502:physiology; D018392:Genomic Imprinting; D006801:Humans; D008297:Male; D051379:Mice; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics / Q000473:pathology*; D009928:Organ Specificity; D018239:Seminoma / Q000235:genetics / Q000473:pathology; D013724:Teratoma / Q000473:pathology; D013736:Testicular Neoplasms / Q000235:genetics / Q000473:pathology