Transmission of germline TP53 mutations from male carriers to female partners

Gestational choriocarcinoma (CC) represents the most aggressive form of gestational tumours. In Europe and North America, gestational CC occurs in approximately 1/50 000 deliveries.1 We report the detection, in a gestational CC developed in a female partner of a patient with Li-Fraumeni syndrome (LFS) (MIM #151623), of the germline TP53 mutation initially detected in this LFS patient. In the French LFS series, we identified 78 fathers who were carriers of a germline TP53 mutation. Among the 213 corresponding pregnancies, we found two other cases of gestational CC in their partners. We estimate that gestational CC occurs in approximately 1% of the deliveries in female partners of TP53 mutation carriers. Gestational trophoblastic disease (GTD), which can occur after either abnormal or normal fertilisation, is characterised by the uncontrolled proliferation of trophoblastic cells normally producing the placenta. GTD includes premalignant (complete and partial hydatidiform moles) and malignant (invasive mole, gestational CC, placental-site trophoblastic and epithelioid trophoblastic tumours) lesions.1 We considered the diagnosis of LFS, a remarkable cancer predisposition characterised by the extent of tumour spectrum,2 in the family described in figure 1. The male index case had developed a cholangiocarcinoma at 37 years of age, …