chromosome 22 in a major percentage of tumor celis, indicating the involvement of a tumor suppressor gene. Although loss of chromosome 22 in tumor tissue might be a secondary effect of tumorigenesis, the consistent observation of loss of chromosome 22 in our and other reported cases, suggest a causal relationship. Because ependymomas are sometimes found in neurofibromatosis type 2, we searched for mutations in the NF2 gene, in RNA from the tumor of patient D. No mutation was detected, thus we have no evidence that the NF2 gene is involved in this family. Howeyer, there are indications for additional loci on chromosome 22 involved in the development of NF2 related tumors. The likely transmission of the disorder by 2 healthy brothers, their exclusively male offspring, the occurrence of spontaneous abortions and the history of a brain tumor in a paternal aunt, raise questions on the possible mode of inherilance. It cannot be explained by simple classic mendelian genetics, and variation in expression of an autosomal dominant gene is a proposed explanation, but lacks precision. Whether sex-related effects of the transmitting parent (imprinting), or a gene with a variable insert size may be involved remains open to speculation, and awaits the isolation and characterization of the gene involved. Rcfel'ences Arnoldus EPJ, Noordermeer lA, Peters AC, Voo,molen JHC, Bots GTAM, Raap AK, van der Ploeg M (1990) Interphase cytogenetics on brain tumors. Genes Chrom Cancer 3: 101-107. van Biezen NA, Lekanne Deprez RH, Thijs A, Heutink p, Ooslra BA, Geurts van Kessel AHM, ZwarthoffEC (1993) Isolation and characterisation of25 unique DNA markers for human chromosome 22. Genomics 15:206- 208. Lekanne Deprez RH, Bianchi AB, Groen NA, Seizinger BR, Hagemeijer A, van Dronen E, Bootsma D, Koper JW, Avemat CJJ, Kley N, Zwarthoff EC (1994) Frequent NF2 gene transcript mutations in sporadic meningiomas and vestibular scbwannomas. Am J Hum Genet 54:1022-1029. Ranson DT, Ritlaml SR, Kimmel DW, Moertel CA, Dabl RJ, Scheithauer BW, Kelly PI Jenkins RB (1992) Cytogenetic and loss of heterozygosity studies in ependymomas, pylocytic astrocytomas and oligodendrogliomas. Genes Chrom Cancer 5:348-356. Salo T, Sbimoda A, Taskahashi T, Kurokawa H, Ando M, Goto S, Takamura H (1984) Congenital anaplastic ependymoma: a case report of familial glioma, Childs Brain 11:342-348. Savard ML, Gilchrist DM (l989)Ependymomas in two sisters and a maternal male cousin with mosaicism with monosomy 22 in tumour. Pediatr Neurosci 15:80-84. Tijssen CC, Halprin MR, Endtz U, Familial brain tumours. Marlinus Nijhoff Publishers 1982. 108
Chapter V A t(4;22) ill a meningioma points to the localization of a Plltative tllmor sllppressor gene Am. J. HUIIl. Genet. 48:783-790, 1991 109
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GENES ON CHROMOSOME 22 INVOLVED IN
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PROMOTmCOMMIssm Promotor: Prof. Dr.
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Contents List of abbreviations 9 Ch
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List of abbreviations APC bp DCC FA
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1 Cancer is a genetic disease It is
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transformation came from somatic ce
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to tumorigenesis if a mutation inac
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is that this interaction inactivate
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endogenous wt p53 by forming mixed
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Recent studies in these families ha
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In about 15% of all colon tumors an
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e explained by assuming that the nu
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3.6 The NFl gene Neurofibromatosis
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4 MENINGIOMA 4.1 Cells of origin In
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fossa and foramen magnum), convexit
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early cell cultures the presence of
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gene (Dumanski et aI., NNFF consort
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et aI., 1991b; Larsson et aI., 1990
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6 References Aaltonen LA, Peltomiik
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(1988) SV40 large tumor antigen for
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Haber DA, Buckler AJ, Glaser T, Cal
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carcinomas. Genes Chrom Cancer 2:19
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Pelletier J, Breunin~ W, Kashtan CE
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Stratton MR, Darling J, Lantos PL,
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Chapter II Isolatioll alld characte
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SHORT COMMUNICATION TABLE 1 Charact
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- Page 65: Chapter III Cytogenetic, molecular
- Page 68 and 69: Introduction Meningiomas are consid
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- Page 131 and 132: Southerll, 1l0l1hern blots and evol
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- Page 137 and 138: postulates that the first AUG codon
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Lebnne Deprez et lli. observed at a
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Summary and Discussion Meningioma i
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translocation (Chapter V). These hy
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were derived from patients with mor
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Samenvatting Meningeomen zUn goedaa
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het gebied rondom het MNI gen te be
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Curriculum vitae 30 juni 1965 gebor
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List of publications I) van 't Veer
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Nawoord Dit boekje is 101 sland gek