Wood merchant Hermann Judey with his first wife Olga Judey nee Fischmann on the coast Portraits Couples

Hermann (Lazar Hirsch) Judey, born 1878 Riga and died 1959 New York; Olga Judey nee Fischmann, 1878-1929

Studio portrait of the wood merchant Hermann Judey with his stepson Paul Portraits Family

Paul was the son from a previous marriage of Hermann's first wife Olga Judey nee Fischmann

Jacob Judey-Barosin and his father Hermann Judey hiking with friends; Sächsische Schweiz Portraits Men

l-r: Martin Lipschitz, Sam Kohn, Hermann Judey, Willy Lipschitz, Georg Eliasberg and Jacob Judey-Barosin

Studio portrait of Hermann (Lazar Hirsch) Judey, his father Joseph (Mitskun) Judey, and Hermann's cousin Vladimir (Valodya) Barosin seated around a chess table; Riga Portraits Family

Hermann (Lazar Hirsch) Judey, born 1878 Riga and died 1959 New York; Joseph (Mitskun) Judey, born 1854 Vilna and died 1931 Berlin

Studio portrait of Hermann (Lazar Hirsch) Judey with his wife Olga Judey nee Fischmann; Berlin Portraits Couples

Hermann (Lazar Hirsch) Judey, born 1878 Riga and died 1959 New York; Olga Judey nee Fischmann, 1878-1929

Studio portrait of Erich von Kahler; Munich.

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Outdoor portrait of Emil Preetorius, Erich von Kahler and Friedrich Gundolf.

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Studio portrait of unidentified Levy brother (most likely Arthur or Hermann) in military uniform; Nogent-Sur-Seine, France.

Photographer's imprint lower left corner

Ambassador von Staden and Secretary Califano signing the U.S.-German Social Security Agreement; Washington, D.C.

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Rudolf and Antoinette von Kahler in living room; Vienna-Doebling Architecture; Residences

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Painting of Freiherr Martin von Magnus Family Portraits Family

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Portrait of Hermann Meyerhof.

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Portrait of Walter Godshaw, Charlie Sloan (Karl-Hermann Solomon), and Ida, Kaete Solomon's maid; Hannover, Germany.

From left to right: Walter Gottschalk, Ida, Charlie Sloan (Karl Hermann Solomon); Ida, Kaete Solomon's maid, nursed Charlie back to health after his release from Dachau

Genetic Mechanisms of Tumourigenesis in von Hippel-Lindau-Associated Tumours with the Emphasis on Capillary Hemangioblastoma

The von Hippel-lindau (VHL) disease is a dominantly inherited neoplastic disorder which predisposes patients to multiple tumours including capillary haemangioblastomas (CHBs), pheochromocytomas (PCCs), renal cell carcinomas (RCCs). CHBs are the most common manifestations of VHL disease, occurring sporadically or as a manifestation of VHL disease. Inactivation of the VHL gene at 3p25-26 is believed to cause both familial and sporadic VHL-associated tumours and germ-line mutation of the VHL gene have been detected in 100% of the CHBs studied. However, a limited number of sporadic CHBs, PCCs display VHL inactivation. Other molecular alterations involved in tumourigenesis of sporadic CHBs, PCCs remain largely unknown. The purpose of the present work was to search for genetic alterations, or other mechanisms of inactivation, in addition to the VHL gene, that may be important in the development of VHL-associated tumours. Though less satisfactory than cure, prevention and early detection are the most promising and feasible means reducing cancer morbidity and mortality. This work is based on the view that increasing knowledge about the molecular events underlying tumour development will eventually aid in early detection and lead to improved treatment. We evaluated a large set of VHL-associated patients, searched for a clinical and radiologic signs of the disease. We succesfully performed a germ-line mutation analysis and characterised three patient groups, VHL, suspect VHL and sporadic, a germ-line mutation analysis revealed a 50% mutation rate only in the VHL groups, no sporadic or suspect cases displayed any mutation. We also utilized comparative genomic hybridization (CGH) to screen for DNA copy number changes in both sporadic and VHL-associated CHB. Our analysis revealed (27%) DNA copy number losses. The most common finding was loss of chromosomal arm 6q, seen in (23%) cases, No differences were noted between VHL-associated and sporadic tumours. Furthermore a loss of heterozygosity (LOH) study on chromosome 3p and 6q was done with the purpose to determine allele losses not observable by CGH, and to uncover the location of putative tumour suppressor genes important in CHB and PCC tumourigenesis. We identified loss of chromosome 6q and a minimal deleted area at 6q23-24 in CHBs. We also showed LOH at 6q23-24 in PCCs and identified the ZAC1 (6q24-25) as a candidate gene, ZAC1 is a maternally imprinted tumour suppressor gene with anti proliferative properties. To study further the role of ZAC inactivation in CHBs, we investigated LOH, promoter hypermethylation and expression status of the ZAC1 gene in mainly sporadic CHBs. Our LOH analysis revealed that the majority of the tumours with allele loss. The gene promoter methylation analysis similarly detected predominance of the methylated ZAC sequence in almost all tumours. Immunohistochemistry exhibited a strongly reduced expression of ZAC in stromal cells of all CHBs studied. Our current results indicate that the absence of the unmethylated, ZAC1 promoter sequence was highly concurrent with LOH for the ZAC1 region or 6q loss. This observation together with lack of ZAC expression, points to preferential loss of the non imprinted, expressed ZAC allele in CHB, in summary, our series of studies reveal a new chromosomal region 6q, emphasizes the importance of ZAC1 gene in the development of CHB and PCC, particularly in non-VHL associated cases.