Characteristic chromosomal aberrations in sporadic cerebellar hemangioblastomas revealed by comparative genomic hybridization

Hemangioblastomas (HBs) of the central nervous system are benign tumors and occur as sporadic (sp) tumors (75%) or as a manifestation of the von Hippe l-Lindau (VHL) disease (25%). VHL-disease is an autosomal dominant disorder characterized by HBs of the central nervous system and retina, renal cell carcinoma (RCC), phaeochromocytoma (PHEO), islet tumors of the pancreas, an d endolympatic sac tumors as well as cysts and cystadenoma in the kidney, p ancreas and epididymis. In VHL patients a large spectrum of germline mutati ons in the VHL gene has been detected. In spHBs VHL alleles are reported to be inactivated in up to 50% of the tumors. To our knowledge the involvemen t of other genes in spHBs has not been investigated. To elucidate the oncog enesis of spHBs, we performed CGH on 10 spHBs to screen for chromosomal imb alances throughout the entire tumor genome. Aberrations most frequently det ected are losses of chromosomes 3 (70%), 6 (50%), 9 (30%), and 18q (30%) an d a gain of chromosome 19 (30%). Based on these frequencies and the co-occu rrence of these aberrations in the analyzed tumors we hypothesize that loss of chromosome 3 (harboring the VHL gene) is an early event in the oncogene sis of spHBs, followed by loss of 6, and then losses of chromosomes 9, 18q and gain of chromosome 19. Comparison of the chromosomal imbalances in spHB s to those previously reported in RCCs and PHEOs reveals that the pathway o f spHBs shows similarities to both the RCCs and PHEOs.