Skip to main content
SpringerLink
Log in

Genetics and Pathogenesis: A Recent Update

  • Chapter
  • First Online:
Gestational Trophoblastic Disease

  • 284 Accesses

Abstract

Gestational trophoblastic diseases (GTDs) are a group of disorders that include molar diseases like partial and complete hydatidiform moles (HMs) as well as neoplastic conditions like invasive mole, placental site trophoblastic tumor, epithelioid trophoblastic tumor, and choriocarcinoma. These lesions arise as a result of uncontrolled proliferation and/or invasion of trophoblastic tissue. HMs are the commonest and best understood lesions of the group. We now know the underlying pathogenetic mechanisms of HMs, a disease that was once considered to arise as a result of consumption of dirty marsh water. Owing to their rarity and paucity of tissue samples, our knowledge of GTNs is relatively limited. However, as our understanding of the disease process has improved, attempts are being made to utilize this information in disease diagnosis and management. Recent research focuses on predicting the progression of hydatidiform moles to GTN, predicting treatment response, and finding out the mechanisms underlying chemoresistance. This chapter aims to outline our current understanding of genetics and pathogenesis of various GTDs and discuss the recent advances.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Shih IM, Kurman RJ. Molecular basis of gestational trophoblastic diseases. Curr Mol Med. 2002;2(1):1–12.

    Article  CAS  PubMed  Google Scholar 

  2. Candelier JJ. The hydatidiform mole. Cell Adh Migr. 2016;10(1–2):226–35.

    Article  PubMed  Google Scholar 

  3. Hoffner L, Surti U. The genetics of gestational trophoblastic disease: a rare complication of pregnancy. Cancer Genet. 2012;205(3):63–77.

    Article  CAS  PubMed  Google Scholar 

  4. Matsuda T, Wake N. Genetics and molecular markers in gestational trophoblastic disease with special reference to their clinical application. Best Pract Res Clin Obstet Gynaecol. 2003;17(6):827–36.

    Article  PubMed  Google Scholar 

  5. Kajii T, Ohama K. Androgenetic origin of hydatidiform mole. Nature. 1977;268:633–4.

    Article  CAS  PubMed  Google Scholar 

  6. Jacobs PA, Hunt PA, Matsuura JS, et al. Complete and partial hydatidiform mole in Hawaii: cytogenetics, morphology and epidemiology. Br J Obstet Gynaecol. 1982;89:258–66.

    Article  CAS  PubMed  Google Scholar 

  7. Wallace DC, Surti U, Adams CW, et al. Complete moles have paternal chromosomes but maternal mitochondrial DNA. Hum Genet. 1982;61:145–7.

    Article  CAS  PubMed  Google Scholar 

  8. Golubovsky MD. Postzygotic diploidization of triploids as a source of unusual cases of mosaicism, chimerism and twinning. Hum Reprod. 2003;18:236–42.

    Article  CAS  PubMed  Google Scholar 

  9. Hoffner L, Parks WT, Swerdlow SH, et al. Simultaneous detection of imprinted gene expression (p57(KIP2)) and molecular cytogenetics (FICTION) in the evaluation of molar pregnancies. J Reprod Med. 2010;55:219–28.

    CAS  PubMed  Google Scholar 

  10. Fisher RA, Nucci MR, Thaker HM, et al. Complete hydatidiform mole retaining a chromosome 11 of maternal origin: molecular genetic analysis of a case. Mod Pathol. 2004;17:1155–60.

    Article  PubMed  Google Scholar 

  11. McConnell TG, Norris-Kirby A, Hagenkord JM, et al. Complete hydatidiform mole with retained maternal chromosomes 6 and 11. Am J Surg Pathol. 2009;33:1409–15.

    Article  PubMed  Google Scholar 

  12. Moglabey YB, Kircheisen R, Seoud M, El Mogharbel N, Van den Veyver I, Slim R. Genetic mapping of a maternal locus responsible for familial hydatidiform moles. Hum Mol Genet. 1999;8:667–71.

    Article  CAS  PubMed  Google Scholar 

  13. Wang CM, Dixon PH, Decordova S, et al. Identification of 13 novel NLRP7 mutations in 20 families with recurrent hydatidiform mole; missense mutations cluster in the leucine-rich region. J Med Genet. 2009;46(8):569–75.

    Article  CAS  PubMed  Google Scholar 

  14. Ogura Y, Sutterwala FS, Flavell RA. The inflammasome: first line of the immune response to cell stress. Cell. 2006;126(4):659–62.

    Article  CAS  PubMed  Google Scholar 

  15. Judson H, Hayward BE, Sheridan E, et al. A global disorder of imprinting in the human female germ line. Nature. 2002;416:539–42.

    Article  CAS  PubMed  Google Scholar 

  16. Kumar V, Abbas AK, Aster JC. Robbins basic pathology. 10th ed. Philadelphia, PA: Elsevier; 2018.

    Google Scholar 

  17. Judson H, Hayward BE, Sheridan E, Bonthron DT. A global disorder of imprinting in the human female germ line. Nature. 2002;416:539–42.

    Article  CAS  PubMed  Google Scholar 

  18. El-Maarri O, Seoud M, Rivière JB, et al. Patients with familial biparental hydatidiform moles have normal methylation at imprinted genes. Eur J Hum Genet. 2005;13:486–90.

    Article  CAS  PubMed  Google Scholar 

  19. Hayward BE, De Vos M, Talati N, et al. Genetic and epigenetic analysis of recurrent hydatidiform mole. Hum Mutat. 2009;30(5):E629–39.

    Article  PubMed  Google Scholar 

  20. Kou YC, Shao L, Peng HH, et al. A recurrent intragenic genomic duplication, other novel mutations in NLRP7 and imprinting defects in recurrent biparental hydatidiform moles. Mol Hum Reprod. 2008;14(1):33–40.

    Article  CAS  PubMed  Google Scholar 

  21. El-Maarri O, Slim R. Familial hydatidiform molar pregnancy: the germline imprinting defect hypothesis? Curr Top Microbiol Immunol. 2006;301:229–41.

    CAS  PubMed  Google Scholar 

  22. Parry DA, Logan CV, Hayward BE, et al. Mutations causing familial biparental hydatidiform mole implicate C6orf221 as a possible regulator of genomic imprinting in the human oocyte. Am J Hum Genet. 2011;89:451–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Kato H, Terao Y, Ogawa M, et al. Growth-associated gene expression profiles by microarray analysis of trophoblast of molar pregnancies and normal villi. Int J Gynecol Pathol. 2002;21:255–60.

    Article  CAS  PubMed  Google Scholar 

  24. Lurain JR. Gestational trophoblastic disease II: classification and management of gestational trophoblastic neoplasia. Am J Obstet Gynecol. 2011;204:11–8.

    Article  PubMed  Google Scholar 

  25. Wake N, Seki T, Fujita H, et al. Malignant potential of homozygous and heterozygous complete moles. Cancer Res. 1984;44:1226–30.

    CAS  PubMed  Google Scholar 

  26. Yang YH, Kwak HM, Park TK, et al. Comparative cytogenetic and clinicopathologic studies on gestational trophoblastic neoplasia, especially hydatidiform mole. Yonsei Med J. 1986;27:250–60.

    Article  CAS  PubMed  Google Scholar 

  27. Xu ML, Yang B, Carcangiu ML, et al. Epithelioid trophoblastic tumor: comparative genomic hybridization and diagnostic DNA genotyping. Mod Pathol. 2009;22:232–8.

    Article  CAS  PubMed  Google Scholar 

  28. Palmer JR. Advances in the epidemiology of gestational trophoblastic disease. J Reprod Med. 1994;39:155–62.

    CAS  PubMed  Google Scholar 

  29. Cheung AN, Zhang HJ, Xue WC, et al. Pathogenesis of choriocarcinoma: clinical, genetic and stem cell perspectives. Future Oncol. 2009;5:217–31.

    Article  CAS  PubMed  Google Scholar 

  30. Kohorn EI. Negotiating a staging and risk factor scoring system for gestational trophoblastic neoplasia. A progress report. J Reprod Med. 2002;47:445–50.

    PubMed  Google Scholar 

  31. Ahmed MN, Kim K, Haddad B, et al. Comparative genomic hybridization studies in hydatidiform moles and choriocarcinoma: amplification of 7q21-q31 and loss of 8p12-p21 in choriocarcinoma. Cancer Genet Cytogenet. 2000;116:10–5.

    Article  CAS  PubMed  Google Scholar 

  32. Matsuda T, Sasaki M, Kato H, et al. Human chromosome 7 carries a putative tumor suppressor gene(s) involved in choriocarcinoma. Oncogene. 1997;15:2773–81.

    Article  CAS  PubMed  Google Scholar 

  33. Asanoma K, Kato H, Inoue T, et al. Analysis of a candidate gene associated with growth suppression of choriocarcinoma and differentiation of trophoblasts. J Reprod Med. 2004;49:617–26.

    CAS  PubMed  Google Scholar 

  34. Alifrangis C, Seckl MJ. Genetics of gestational trophoblastic neoplasia: an update for the clinician. Future Oncol. 2010;6(12):1915–23.

    Article  PubMed  Google Scholar 

  35. Sebire NJ, Seckl MJ. Gestational trophoblastic disease: current management of hydatidiform mole. BMJ. 2008;337:1193.

    Article  Google Scholar 

  36. Kajii T, Kurashige H, Ohama K, et al. XY and XX complete moles: clinical and morphologic correlations. Am J Obstet Gynecol. 1984;150:57–64.

    Article  CAS  PubMed  Google Scholar 

  37. Wake N, Fujino T, Hoshi S, et al. The propensity to malignancy of dispermic heterozygous moles. Placenta. 1987;8:319–26.

    Article  CAS  PubMed  Google Scholar 

  38. Fisher RA, Lawler SD. Heterozygous complete hydatidiform moles: do they have a worse prognosis than homozygous complete moles? Lancet. 1984;2:51.

    Article  CAS  PubMed  Google Scholar 

  39. Mutter GL, Pomponio RJ, Berkowitz RS, et al. Sex chromosome composition of complete hydatidiform moles: relationship to metastasis. Am J Obstet Gynecol. 1993;168:1547–51.

    Article  CAS  PubMed  Google Scholar 

  40. Cheung AN, Sit AS, Chung LP, et al. Detection of heterozygous XY complete hydatidiform mole by chromosome in situ hybridization. Gynecol Oncol. 1994;55:386–92.

    Article  CAS  PubMed  Google Scholar 

  41. van de Kaa CA, Schijf CP, de Wilde PC, et al. Persistent gestational trophoblastic disease: DNA image cytometry and interphase cytogenetics have limited predictive value. Mod Pathol. 1996;9:1007–14.

    PubMed  Google Scholar 

  42. Fisher RA, Hodges MD. Genomic imprinting in gestational trophoblastic disease review. Placenta. 2003;24:S111–8.

    Article  PubMed  Google Scholar 

  43. Kaneki E, Kobayashi H, Hirakawa T, et al. Incidence of postmolar gestational trophoblastic disease in androgenetic moles and the morphological features associated with low risk postmolar gestational trophoblastic disease. Cancer Sci. 2010;101:1717–21.

    Article  CAS  PubMed  Google Scholar 

  44. Niemann I, Hansen ES, Sunde L. The risk of persistent trophoblastic disease after hydatidiform mole classified by morphology and ploidy. Gynecol Oncol. 2007;104:411–5.

    Article  PubMed  Google Scholar 

  45. Smith HO. Gestational trophoblastic disease epidemiology and trends. Clin Obstet Gynecol. 2003;46(3):541–56.

    Article  PubMed  Google Scholar 

  46. McNeish IA, Strickland S, Holden L, et al. Low-risk persistent gestational trophoblastic disease: outcome after initial treatment with low-dose methotrexate and folinic acid from 1992 to 2000. J Clin Oncol. 2002;20(7):1838–44.

    Article  CAS  PubMed  Google Scholar 

  47. Bower M, Newlands ES, Holden L, et al. EMA/CO for high-risk gestational trophoblastic tumors: results from a cohort of 272 patients. J Clin Oncol. 1997;15(7):2636–43.

    Article  CAS  PubMed  Google Scholar 

  48. Chen Y, Qian H, Wang H, et al. Ad-PUMA sensitizes drug-resistant choriocarcinoma cells to chemotherapeutic agents. Gynecol. Oncology. 2007;107(3):505–12.

    CAS  Google Scholar 

  49. Kobel M, Pohl G, Schmitt WD, Hauptmann S, Wang TL, IEM S. Activation of mitogen-activated protein kinase is required for migration and invasion of placental site trophoblastic tumor. Am J Pathol. 2005;167(3):879–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Mparmpakas D, Zacharides E, Foster H, Harvey A. Expression of mTOR and downstream signalling components in the JEG-3 and BeWo human placental choriocarcinoma cell lines. Int J Mol Med. 2010;25(1):65–9.

    CAS  PubMed  Google Scholar 

  51. Tuncer ZS, Vegh GL, Fulop V, Genest DR, Mok SC, Berkowitz RS. Expression of epidermal growth factor receptor-related family products in gestational trophoblastic diseases and normal placenta and its relationship with development of postmolar tumor. Gynecol Oncol. 2000;77(3):389–93.

    Article  CAS  PubMed  Google Scholar 

  52. Sarkar S, Kacinski BM, Kohorn EI, et al. Demonstration of myc and ras oncogene expression by hybridization in situ in hydatidiform mole and in the BeWo choriocarcinoma cell line. Am J Obstet Gynecol. 1986;154:390–3.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of O & G, UCMS, New Delhi, India

    Shalini Rajaram

  2. Department of Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

    Divya Aggarwal

Authors
  1. Shalini Rajaram
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Divya Aggarwal
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Associate Professor, Department of Gynaecologic Oncology, Acharya Harihar Post Graduate Institute of Cancer, Cuttack, India

    Bhagyalaxmi Nayak

  2. Professor & Head, Department of Obstetrics and Gynecology, King George’s Medical University, Lucknow, India

    Uma Singh

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Rajaram, S., Aggarwal, D. (2021). Genetics and Pathogenesis: A Recent Update. In: Nayak, B., Singh, U. (eds) Gestational Trophoblastic Disease. Springer, Singapore. https://doi.org/10.1007/978-981-33-4878-3_3

Download citation

  • DOI: https://doi.org/10.1007/978-981-33-4878-3_3

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-33-4877-6

  • Online ISBN: 978-981-33-4878-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation