gms | German Medical Science

Objective: Cranial hemangiopericytomas are rare tumors of mesenchymal origin with a high proclivity towards recurrence and extraneural metastasis. Total tumor resection is the main treatment of choice due to its radiochemical resistant nature. Considering the paucity of reports dealing with the tumor genetics and epigenetics of cranial hemangiopericytomas and the still ongoing debate about their histological standing, we examined a series of 9 cranial hemangiopericytomas for the most important meningioma and glioma specific cytogenetic and epigenetic aberrations

Method: In a total of nine histopathologically confirmed cranial hemangiopericytoma, this study evaluates the promoter methylation status of p15(CDKN2B), p16INK4A, TIMP3, MGMT and NDRG2 genes which have been shown to be epigenetically altered in meningiomas and gliomas, respectively. Furthermore, typical numerical chromosomal aberrations reported in meningiomas and gliomas were investigated using two-color fluorescent in situ hybridization (FISH) on touch-preparations with locus specific probe pairs detecting 1p36/22q11, 14q24/18q21, and 9p21/10q23. Additionally, numeric alterations of chromosome 7 were assessed by an indirect FISH approach using a centromeric probe.

Results: All studied cases presented with an unmethylated status of the p15, MGMT and TIMP3 promoters. One specimen was encountered with positive methylation signal for p16 in methylation specific PCR analysis. Direct bisulfite sequencing for NDRG2 revealed only in 1/6 cases a moderately elevated average methylation degree. In FISH analyses, disomy for all targeted chromosomal regions was found in 5/9 studied hemangiopericytoma specimens; in two tumors an oligocellular clone with hemizygous loss of 10q23 was detected. In one other specimen, virtually all nuclei harbored a hemizygous deletion of 9p21. One further cranial hemangiopericytoma was characterized by a tetraploid mainline with slight sidelines that contained trisomies of 9p21 and 10q23.

Conclusions: This work shows that most cranial hemangiopericytomas obviously lack glioma and meningioma specific epigenetic and molecular cytogenetic lesions, further providing evidence that cranial hemangiopericytomas represent a distinct tumor entity with genetic different features especially from meningiomas. These present findings prompt one to speculate about the possible role of inactivation of p16INK4a and deletions on 10q in the underlying tumorigenesis of a distinct subgroup of cranial hemangiopericytomas.