Abstract
Choriocarcinoma is a highly malignant neoplasm resulting from the malignant transformation of proliferating trophoblastic cells and the molecular mechanisms leading to this transformation remain to be characterized. We report here the first case of a female germline TP53 mutation carrier who developed, as a first tumour, a lung choriocarcinoma, 6 months after a normal delivery. Molecular analyses established the gestational origin of the choriocarcinoma and showed, within the tumour, the presence of the germline mutant TP53 allele and loss of the wild-type allele. Resistance to methotrexate chemotherapy led to perform a surgical resection of the tumour. In agreement with the permissive role of TP53 mutations to oncogenic events, this report strongly suggests that TP53 mutations may promote malignant transformation of proliferating trophoblastic cells. Therefore, female TP53 mutation carriers may have an increased risk of developing gestational choriocarcinoma and might benefit from β-hCG level monitoring after pregnancy.
This is a preview of subscription content, log in via an institution to check access.
Abbreviations
- CC:
-
Choriocarcinoma
- GCC:
-
Gestational choriocarcinoma
- LFS:
-
Li-Fraumeni syndrome
References
Seckl MJ, Sebire NJ, Fisher RA, Golfier F, Massuger L, Sessa C, ESMO Guidelines Working Group (2013) Gestational trophoblastic disease: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 24(Suppl 6):vi39–50. doi:10.1093/annonc/mdt345
Tempfer C, Horn L-C, Ackermann S et al (2016) Gestational and non-gestational trophoblastic disease. Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Registry No. 032/049, December 2015). Geburtshilfe Frauenheilkd 76(2):134–144
Fisher RA, Savage PM, MacDermott C et al (2007) The impact of molecular genetic diagnosis on the management of women with hCG-producing malignancies. Gynecol Oncol 107(3):413–419
Zhao J, Xiang Y, Wan XR et al (2009) Molecular genetic analyses of choriocarcinoma. Placenta 30(9):816–820. doi:10.1016/j.placenta.2009.06.011
Kamihara J, Rana HQ, Garber JE (2014) Germline TP53 mutations and the changing landscape of Li-Fraumeni syndrome. Hum Mutat 35(6):654–662. doi:10.1002/humu.22559
Bougeard G, Renaux-Petel M, Flaman J-M et al (2015) Revisiting Li-Fraumeni syndrome from TP53 mutation carriers. J Clin Oncol 33(21):2345–2352. doi:10.1200/JCO.2014.59.5728
Kamata S, Sakurada A, Sato N, Noda M, Okada Y (2016) A case of primary pulmonary choriocarcinoma successfully treated by surgery. Gen Thorac Cardiovasc Surg. doi:10.1007/s11748-016-0666-8
Malkin D, Jolly KW, Barbier N et al (1992) Germline mutations of the p53 tumor-suppressor gene in children and young adults with second malignant neoplasms. N Engl J Med 326(20):1309–1315
Patrier-Sallebert S, Bougeard G, Baert-Desurmont S et al (2015) Transmission of germline TP53 mutations from male carriers to female partners. J Med Genet 52(3):145–146. doi:10.1136/jmedgenet-2014-102853
Shi YF, Xie X, Zhao CL et al (1996) Lack of mutation in tumour-suppressor gene p53 in gestational trophoblastic tumours. Br J Cancer 73(10):1216–1219
Acknowledgements
The authors thank the French National Cancer Institute (INCa) for funding and Philippe Denizeau for providing clinical data.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare no conflict of interest.
Rights and permissions
About this article
Cite this article
Brehin, AC., Patrier-Sallebert, S., Bougeard, G. et al. Gestational choriocarcinoma associated with a germline TP53 mutation. Familial Cancer 17, 113–117 (2018). https://doi.org/10.1007/s10689-017-9996-7
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10689-017-9996-7