Germ cell tumor causes

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  • The cause of germ cell tumor is not understood fully but there are many risk factors that believed to play a role in the development of germ cell tumors.
Germ cell tumor causes
General Causes
Dysgerminoma
Seminoma Common causes
  • Cryptorchidism
  • Undescended testis
  • Abdominal testis
  • Trauma
  • Mumps
  • Maternal estrogen exposure
  • Genetic Causes
  • Seminoma is caused by a mutation in the KIT gene.
  • 12p11.2-p12.1 chromosomal amplifications and deletions observed in majority of cases.


Embryonal cell carcinoma
Choriocarcinoma
Yolk sac tumor




  • Individuals with Differences of Sex Development (DSDs) are predisposed to gonadal germ cell tumor (GCT)[1]
  • To determine the risk of Germ cell tumor in patients with DSDs, we need to categorize DSDs precisely based on karyotype, molecular data, hormonal milieu, external phenotype and gonadal morphology[1]
  • Common causes of seminoma may include:[2][3]
  • Cryptorchidism
  • Undescended testis
  • Abdominal testis
  • Trauma
  • Mumps
  • Maternal estrogen exposure
  • Genetic Causes
  • Seminoma is caused by a mutation in the KIT gene.
  • 12p11.2-p12.1 chromosomal amplifications and deletions observed in majority of cases.
  • There are no established causes for germinoma. However, several theories have been postulated to define the cause of germ cell tumors.
  • GCTs arise from primordial germ cells that migrate to the germinal ridges in the developing embryo. The process of migration appears to be under the control of complex molecular events.
  • Alteration in any of these molecular pathways may give rise to GCTs. Rather than laterally to genital ridges, some primordial germ cells that have left the yolk sac endoderm migrate aberrantly cranially towards the diencephalic midline structures.[4][5][6][7][8][9][10]
  • Important factors in cell migration include the following:
    • Extracellular matrix
    • Chemotropic factors
    • Tumor growth factor beta 1
  • Since the maturation of the fetal hypothalamus coincides with the migration of primordial germ cells, the fetal hypothalamus may secrete chemotrophic factors that attract primordial germ cells to the diencephalon.


There are no established causes for ovarian germ cell tumors

Common causes of seminoma may include:


Genetic Causes

Seminoma is caused by a mutation in the KIT gene

12p11.2-p12.1 chromosomal amplifications and deletions observed in majority of cases


Choriocarcinoma


The etiology of yolk sac tumors (YSTs) is essentially unknown. It is speculated that hypermethylation of the RUNX3 gene promoter and overexpression of GATA-4, a transcription factor that regulates differentiation and function of yolk sac endoderm, may play important roles in the pathogenesis of yolk sac tumors (YSTs)





References

  1. 1.0 1.1 Pyle LC, Nathanson KL (2017). "A practical guide for evaluating gonadal germ cell tumor predisposition in differences of sex development". Am J Med Genet C Semin Med Genet. 175 (2): 304–314. doi:10.1002/ajmg.c.31562. PMC 5538907. PMID 28544305.
  2. Ferguson L, Agoulnik AI (2013). "Testicular cancer and cryptorchidism". Front Endocrinol (Lausanne). 4: 32. doi:10.3389/fendo.2013.00032. PMID 23519268.
  3. Merzenich H, Ahrens W, Stang A, Baumgardt-Elms C, Jahn I, Stegmaier C, Jöckel KH (December 2000). "Sorting the hype from the facts in testicular cancer: is testicular cancer related to trauma?". J. Urol. 164 (6): 2143–4. PMID 11061944.
  4. Echevarría ME, Fangusaro J, Goldman S (2008). "Pediatric central nervous system germ cell tumors: a review". Oncologist. 13 (6): 690–9. doi:10.1634/theoncologist.2008-0037. PMID 18586924.
  5. Jubran RF, Finlay J (2005). "Central nervous system germ cell tumors: controversies in diagnosis and treatment". Oncology (Williston Park). 19 (6): 705–11, discussion 711-2, 715–7, 721. PMID 15971448.
  6. Palmer RD, Foster NA, Vowler SL, Roberts I, Thornton CM, Hale JP; et al. (2007). "Malignant germ cell tumours of childhood: new associations of genomic imbalance". Br J Cancer. 96 (4): 667–76. doi:10.1038/sj.bjc.6603602. PMC 2360055. PMID 17285132.
  7. Sato K, Takeuchi H, Kubota T (2009). "Pathology of intracranial germ cell tumors". Prog Neurol Surg. 23: 59–75. doi:10.1159/000210053. PMID 19329861.
  8. Pereda J, Motta PM (1991). "A unique fibrillar coat on the surface of migrating human primordial germ cells". Arch Histol Cytol. 54 (4): 419–25. PMID 1760220.
  9. Godin I, Wylie CC (1991). "TGF beta 1 inhibits proliferation and has a chemotropic effect on mouse primordial germ cells in culture". Development. 113 (4): 1451–7. PMID 1811953.
  10. Horowitz MB, Hall WA (1991). "Central nervous system germinomas. A review". Arch Neurol. 48 (6): 652–7. PMID 2039390.

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