Brehin Anne-Claire, Patrier-Sallebert Sophie, Bougeard Gaëlle, Side-Pfennig Gwendoline, Llamas Gutierrez Francisco, Lamy Aude, Colasse Elodie, Kandel-Aznar Christine, Delnatte Capucine, Vuillemin Eric, Sadot-Lebouvier Sophie, Odent Sylvie, Sabourin Jean-Christophe, Golfier François, Frebourg Thierry
Department of Pathology, Normandy Centre for Genomic and Personalized Medicine, Normandie University, UNIROUEN, Inserm U1245 and Rouen University Hospital, F 76000, Rouen, France.
Department of Genetics, Normandy Centre for Genomic and Personalized Medicine, Normandie University, UNIROUEN, Inserm U1245 and Rouen University Hospital, F 76000, Rouen, France.
Fam Cancer. 2018 Jan;17(1):113-117. doi: 10.1007/s10689-017-9996-7.
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.
绒毛膜癌是一种由增殖的滋养层细胞恶性转化形成的高度恶性肿瘤，导致这种转化的分子机制仍有待阐明。我们在此报告首例女性种系TP53突变携带者，她在正常分娩6个月后，首次发生了肺绒毛膜癌。分子分析确定了绒毛膜癌的妊娠起源，并显示肿瘤内存在种系突变型TP53等位基因，野生型等位基因缺失。对甲氨蝶呤化疗的耐药导致了肿瘤的手术切除。鉴于TP53突变对致癌事件的促进作用，本报告强烈提示TP53突变可能促进增殖的滋养层细胞的恶性转化。因此，女性TP53突变携带者发生妊娠绒毛膜癌的风险可能增加，妊娠后可能受益于β-hCG水平监测。
