Intracranial germ cell tumors: association with Klinefelter syndrome and sex chromosome aneuploidies

Intracranial germ cell tumors (ICGCTs) occur mainly in male children and adolescents. Polyploidy of the X chromosome and X hypomethylation have been suggested as mechanisms of malignant transformation independently of the histological tumor type. On the other hand, several reports associate these tumors with Klinefelter's syndrome (KS). Recent reports indicate that KS patients have an increased relative risk for development of malignant mediastinal germ cell tumors and also around 8% of male patients with primary mediastinal tumors have KS. In an attempt to explore the frequency of KS amongst patients with ICGCTs and to confirm the presence of X chromosome polyploidies in these tumors, we studied 13 young male patients with ICGCTs. Paraffin-embedded tumoral and normal tissues were studied by FISH. KS was found in 15% of the cases, demonstrating that this constitutive aneuploidy may be related to carcinogenesis. When tumor and non-tumor tissues were compared, statistically significant X and Y chromosome polyploidies in tumors were revealed. These results emphasize that aneuploidies are involved in ICGCT tumorigenesis.