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Lekanne Deprez et a!. Figure I Basic stem·line brytlt)'pe of meningioma 32 (MN32): 45, XY, -I, 4p+, 22q-, 22q+. Arrows indicJte structurJI .1bnormalities (Q-b.mding). Insert shows the normal Jnd JberrJnt ,hromosomes from p.lirs 4, 22, Jnd I (R-bJnding). 022515 (results not shown). This indicates that sequences on 22q distal to 02251 are indeed present on the 4p + marker. To investigate the possibility of a balanced translocation t(4;22), we hybridized the same blots with probes located on 4p16. Probe D4562, which has been located at position 4p16.2- 16.1, recognizes a 2.4-kb fragment in both placental and 14G-1O lanes (fig. 3C). This suggests that sequences up to position 4p16.2 are still retained on the 4p + marker chromosome. Probe F5.53 (fig. 3D) recognizes in placental DNA the cognate fragment of 6.5 kb and a cross-hybridizing band at 3.4 kb. Both bands were mapped on chromosome 4, at positions 4p16.3 (6.5 kb) and 4pI6.1-1S.1 (3.4 kb) (G. J. van Ommen, personal communication). The 3.4-kb band is also present in lane 14G-1O. Thus, sequences from 4p16.1-15.1 are retained on the 4p + chromosome, a finding which confirms the results obtained with probe D4562. The cognate 6.5-kh band is found in hybrid 6A, suggesting that this part of chromosome 4 has been translocated to the 22q - marker chromosome. This conclusion was confirmed by the finding that probe 045125 (located at 4p16.3) also hybridizes to DNA from hybrid 6A but not to that from 14G-I0 (result not shown). The same reciprocal marker segregation pattern was observed with the other hybrid cell lines. Thus, t,lken together the hybridization results strongly suggest that the4p + and 22q - markerchromosomes are indeed the products of a reciprocal translocation t(4;22) (p16;qU). Figure 4A shows an outline of the position of the probes on chromosomes 4 and 22, and in figure 4B their position on the translocation products is indicated. Hybridizations with 25 other single-copy probes for chromosome 22 (N. A. van Biezen, unpublished data) showed that all probes 114
Putative Tumor-suppressor Gene in Meningioma M pi ratio, abl 1.67 bcr ND D2281 1.86 D22815 3.34 D228201 3.80 Figure 2 Ancllpis of cop}' numher of different probes in 1-.INJ2.laneM, DNA isolJ[edfrom r-.INJ2.lanepl,DNA isolJ[ed from J hUIll,ln p!,J.(~ntJJ ~(mtf{}1 DNA. Also indicated is the ratio uf [he JreJ under the CI]n·e of placental Jnd MN.U sign.ll, after densitometric scanning. ND = not done. could be located either on the 4p + or on the 22qchromosomes (results not shown). This finding underlines the conclusion that the t(4;22) is indeed reciprocal and that no substantial parts of chromosome 22 appear to be missing. Discussion A kb ---_., 0 "' '" "' kb B ., ~ , ii "' OJ '" ..
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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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Appendix A lIew polymorphic probe 0
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Nudeic Acids Research, Vol. 19, No.
Page 65: Chapter III Cytogenetic, molecular
Page 68 and 69: Introduction Meningiomas are consid
Page 70 and 71: defined by evaluating 6 histologica
Page 72 and 73: number of clonal chromosomal abnorm
Page 74 and 75: #22 status No. Sex/Age (yr) Site of
Page 76 and 77: #22 slattls No. SexiAge (yr) Site o
Page 78 and 79: #22 status No. Sex/Age (yr) Site of
Page 80 and 81: Table 2. Comparison of FISH, cytoge
Page 82 and 83: No. Days in Karyotypes andlor clona
Page 84 and 85: No. Days in Karyotypes and/or clona
Page 86 and 87: to map both breakpoints (data not s
Page 88 and 89: Statistical analyses concerning age
Page 90 and 91: Tuble 4. Frequency tables between d
Page 92 and 93: from adult patients, indicating tha
Page 94 and 95: Acknowledgements This study was sup
Page 96 and 97: McDermid HE, Duncan AMV, Higgins MJ
Page 99 and 100: Chapter IV Familial anaplastic epen
Page 101 and 102: Familial anaplastic ependymoma: evi
Page 103 and 104: PATIENT A, born 1977, presented at
Page 105 and 106: Microscopic examination (patients A
Page 107 and 108: (Lekanne Deprez et aI., 1994). Tabl
Page 109 and 110: Chapter V A t(4;22) ill a meningiom
Page 111 and 112: Am. J. HI/m. Genet. 48:783-790, 199
Page 113: Putative Tumor-suppressor Gene in M
Page 117 and 118: Putative Tumor-suppressor Gene in M
Page 119 and 120: Chapter VI Molecular clolling of a
Page 121 and 122: Molecular Cloning of a Gene Disrupt
Page 123 and 124: to playa role in the development of
Page 125 and 126: total sheared human genomic DNA bef
Page 127 and 128: Genomic cosmid contig spanning the
Page 129 and 130: probe A is conserved in hamster DNA
Page 131 and 132: Southerll, 1l0l1hern blots and evol
Page 133 and 134: The evolutionary conservation of th
Page 135 and 136: A " l ... aGAP~RAGC EPOV~SR~AGQGE ;
Page 137 and 138: postulates that the first AUG codon
Page 139 and 140: Bijlsma EK, Brouwer~Mladin R, Bosch
Page 141 and 142: Tanaka N, Nishisho I, Yamamoto 1'.1
Page 143 and 144: Chapter VII Constitutional DNA-leve
Page 145 and 146: GENES, CHROMOSOMES & CANCER 9;124-1
Page 147 and 148: LfKANNf DfPREZ fT AL TABLE I. Cytog
Page 149 and 150: LEKANNE DEPRF2 ET AL could be that
Page 151 and 152: Chapter VIII Frequent NF2 gene tran
Page 153 and 154: Am.'. HIIIII. Gellet. 54:1022-1029,
Page 155 and 156: Lekanne Deprez ct al. Table I Oligo
Page 157 and 158: Table 2 Nfl Gene-Transcript Mutatio
Page 159 and 160: Lebnne Deprez et lli. observed at a
Page 161 and 162: Summary and Discussion Meningioma i
Page 163 and 164: 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
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