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Molecular and chemical neuropathology

, Volume 21, Issue 2–3, pp 189–217 | Cite as

Analysis of chromosome 22 loci in meningioma

Alterations in the leukemia inhibitory factor (LIF) locus
  • Robert G. Pergolizzi
  • Susan H. Erster
Article

Abstract

Meningiomas are typically benign tumors arising from arachnoidal cells at the base of the brain. Meningioma is thought to result from the loss or inactivation of a putative tumor suppressor gene located on chromosome 22. We analyzed a set of meningioma DNA specimens by Southern blot hybridization with chromosome 22-specific probes and by PCR using oligomer primers and probes specific to the leukemia inhibitory factor (LIF) gene. Southern analysis suggested that a subset of our specimens are monosomic for 22q11-qter and may have lost one entire copy of chromosome 22. The gene(s) involved in the etiology of meningioma has been localized to 22q11.2-12.3. The locus encoding LIF, a factor that affects the differentiation and proliferation of numerous cell types, has also been localized to this region, at 22q12.1-12.2. The partial overlap of these loci, coupled with the known involvement of the LIF gene product in growth and differentiation, suggested that the LIF locus may be associated with the meningioma defect. We have examined the LIF locus in meningioma specimens at the molecular level by PCR, and by DNA and RNA gelblot hybridizations. Alterations in the structure and/or expression of the LIF locus were detected in several specimens, including the subset that were shown to be monosomic for 22q. All of our tumor specimens were shown to be undermethylated at the LIF locus relative to constitutional DNA from the same patients. Sequence analysis of LIF cDNA from a meningioma revealed the existence of a novel, alternatively spliced LIF mRNA. These results suggest that the LIF gene may be near the putative tumor suppressor locus associated with the development of this phenotype.

Index Entries

Meningioma leukemia inhibitory factor (LIF) chromosome 22 methylation alternative splicing polymerase chain reaction 

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References

  1. Abe E., Ishimi Y., Takahashi N., Akatsu T., Ozawa H., Yaman H., Yoshiki S., and Suda T. (1988) A differentation-inducing factor produced by the osteoblastic cell line MC-3T3-1 stimulates bone resorption by promoting osteoclast formation.J. Bone Min. Res. 3, 635–645.Google Scholar
  2. Barker D., Wright E., Nguyen K., Cannon L., Fain P., Goldgar D., Bishop D. T., Carey J., Baty B., Kivlin J., Willard H., Waye J. S., Grieg G., Leinward L., Nakamura Y., O’Connell P., Leppart M., Lalouel J-M., White R., and Skolnick M. (1987) Gene for Von Recklinghausen neurofibromatosis is in the pericentric region of chromosome 17.Science 236, 1100–1102.PubMedGoogle Scholar
  3. Baumann H. and Wong G. G. (1989) Hepatocyte stimulating factor III shares structural and functional identify with leukemia inhibitory factor.J. Immunol. 143, 1163–1167.PubMedGoogle Scholar
  4. Baylin S. B., Hoppener J. W. M., de Bustros A., Steenbergh P. H., Lips C. J. M., and Nelkin B. D. (1986) DNA methylation patterns of the calcitonin gene in human lung cancers and lymphomas.Cancer Res. 46, 2917–2922.PubMedGoogle Scholar
  5. Baylin S. B., Fearon E. R., Vogelstein B., de Bustros A., Sharkis S. J., Burke P. J., Stahl S. P., and Nelkin B. D. (1987) Hypermethylation of the 5′ region of the calcitonin gene is a property of human lymphoid and acute myeloid malignancies.Blood 70, 412–417.PubMedGoogle Scholar
  6. Bolger G. B., Stamberg J., Kirsch I. R., Hollis G. F., Schwartz D. F., and Thomas G. H. (1985) Chromosome translocation t(14;22) and oncogene (c-sis) variant in a pedigree with familial meningioma.N. Eng. J. Med. 312, 564–567.Google Scholar
  7. Breitbart R. E., Andreadis A., and Nadal-Ginard B. (1987) Alternative splicing: A ubiquitous mechanism for the generation of multiple protein isoforms from single gene.Annu. Rev. Biochem. 56, 467–495.PubMedGoogle Scholar
  8. Budarf M., Sellinger B., Griffen C., and Emmanuel B. S. (1989) Comparative mapping of the constitutional and tumor-associated 11;22 translocations.Am. J. Hum. Genet. 45, 128–139.PubMedPubMedCentralGoogle Scholar
  9. Budarf M., Emmanuel B. S., Mohandas T., Goeddel D. V., and Lowe D. G. (1989a) Human differentiation-stimulating factor (leukemia inhibitory factor, human interleukin DA) gene maps distal to the Ewing sarcoma breakpoint of 22q.Cytogenet. Cell Genet. 52, 19–22.PubMedGoogle Scholar
  10. Bussinger M., Hurst J., and Flavell R. A. (1983) DNA methylation and the regulation of globin gene expression.Cell 34, 197–203.Google Scholar
  11. Casalone R., Simi P., Granata P., Minelli P., Gudici A., Butti G., and Solero C. L. (1990) Correlation between cytogenetic and histopathological findings in 65 human meningiomas.Cancer Genet. Cytogenet. 45, 237–243.PubMedGoogle Scholar
  12. Cedar H. (1988) DNA methylation and gene activity.Cell 53, 3,4.PubMedGoogle Scholar
  13. Cavenee W. K., Dryja T. P., Phillips R. A., Benedict W. F., Godbout R., Gallie B. L., Murphree A. L., Strong L. C., and White R. L. (1983) Expression of recessive alleles by chromosomal mechanisms in retinoblastoma.Nature 305, 779–784.PubMedGoogle Scholar
  14. Chandler L. A., de Clerck C. A., Bogenmann E., and Jones P. A. (1986) Patterns of DNA methylation and gene expression in human tumor cell lines.Cancer Res. 46, 2944–2949.PubMedGoogle Scholar
  15. Deprez R. H. L., Groen N. A., van Biezen N. A. Hagemeijer A., Van Drunun E., Koper J. W., Avwezaat C. J. J., Bootsma D., and Awarthoff E. C. (1991) A t(4;22) in a meningioma point to the localization of a putative tumor suppressor gene.Am. J. Hum. Genet. 48, 783–790.Google Scholar
  16. Dumanski J. P., Rouleau G. A., Nordenskjold M., and Collins V. P. (1990) Molecular genetic analysis of chromosome 22 in 81 cases of meningioma.Cancer Res. 50, 5863–5867.PubMedGoogle Scholar
  17. El-Deiry W. S., Nelkin B. D., Celano P., Chiu Yen R. W., Falco J. P., Hamilton S. R., and Baylin S. B. (1991) High expression of the DNA methylatransferase gene characterizes human neoplastic cells and progression stages of colon cancer.Proc. Natl. Acad. Sci. USA 88, 3470–3474.PubMedGoogle Scholar
  18. Fiedler W., Claussen U. Ludecke H., Senger G., Horsthemke B., van Kessel A. G., Goertzen W., and Fahsold R. (1991) New markers for the neurofibromatosis-2 region generated by microdissection of chromosome 22.Genomics 10, 786–791.PubMedGoogle Scholar
  19. Feinberg A. P. and Vogelstein B. (1983) Hypomethylation distinguishes genes of some human cancers from their normal counterparts.Nature 301, 89–92.PubMedGoogle Scholar
  20. Feinberg A. P., Gehrke C. W., Kuo K. C., and Ehrlich M. (1988) Reduced genomic 5-methylcytosine content in human colonic neoplasia.Cancer Res. 48, 1159–1161.PubMedGoogle Scholar
  21. Fountain J. W., Wallace M. R., Bruce M. S., Seizinger B. R., Menon A. G., Gusella J. F., Michels V. V., Schmidt M. A., Dewald G. W., and Collins F. S. (1989) Physical mapping of a translocation breakpoint in neurofibromatosis.Science 244, 1085–1087.PubMedGoogle Scholar
  22. Gearing D. P., King J. A., and Gough N. M. (1988) Complete sequence of murine myeloid leukemia inhibitory factor.Nucleic Acids Res. 16, 1989)Google Scholar
  23. Gilliand G., Perrin S., and Bunn H. F. (1990) inPCR Protocols: A Guide to Methods and Applications Innis A., Gelfand D. H., Sninsky J. J., and White T. J., eds. Academic Press, Orlando, FL, pp. 60–69.Google Scholar
  24. Godard A., Gascan H., Naulet J., Peyrat M. A., Jacque Y., Soulillon J. P., and Moreau J. F. (1987) Biochemical characterization of HILDA, a human lymphokine active on eosinophils and bone marrow cells.Blood 71, 1618–1623.Google Scholar
  25. Gough N. M., Hilton D. J., Gearing D. P., Willson T. A., King J. A., and Metcalf D. (1988) Biochemical characterization of murine leukema inhibitory factor produced by Krebs ascites and by yeast cells.Blood Cells 14, 431–442.PubMedGoogle Scholar
  26. Gough N. M., Gearing D. P., King J. A., Willson T. A., Hilton D. J., Nicola N. A. and Metcalf D. (1988a) Molecular cloning and expression of the human homologue of the murine gene encoding myeloid leukemia inhibitory factor.Proc. Natl. Acad. Sci. USA 85, 2623–2627.PubMedGoogle Scholar
  27. Green A. R. and Wyke J. A. (1985) Anti-oncogenes: A subset of regulatory genes involved in carcinogenesis.Lancet 2, 475–477.PubMedGoogle Scholar
  28. Gusella J. F., Wexler N. S., Conneally P. M., Naylor S. L., Anderson M. A., Tanzi R. E., Watkins P. C., Ottima K., Wallace M. R., Sakaguchi A. Y., Young A. B., Shoulsen I., Bonilla E., and Martin J. B. (1983) A polymorphic DNA marker genetically linked to Huntington’s disease.Nature 306, 234–238.PubMedGoogle Scholar
  29. Guthrie B. L., Ebersold M. J., Scheithauer B. N., and Shaw E. G. (1989) Meningial hemangiopericytoma: Histopathological features, treatment, and the long term follow up to 44 cases.Neurosurgery 25, 514–522.PubMedGoogle Scholar
  30. Hilton D. J., Nicola N. A., and Metcalf D. (1988) Purification of a murine leukemia inhibitory factor from Krebs ascites cells.Anal. Biochem. 173, 359–376.PubMedGoogle Scholar
  31. Hilton D. J., Nicola N. A., Metcalf D. (1988a) Specific binding of murine leukemia inhibitory factor to normal and leukemia monocytic.Cells. Proc. Natl. Acad. Sci. USA 85, 5971–5975.PubMedGoogle Scholar
  32. Holliday R. (1987) The inheritance of epigenetic defects.Science 238, 163–170.PubMedGoogle Scholar
  33. Kikuchi H. and Hatanaka M. (1990) Gene expression of fibroblast growth factors in human gliomas and meningiomas: Demonstration of cellular source of basic fibroblast growth factor mRNA and peptide in tumor tissue.Proc. Natl. Acad. Sci. USA 87, 5710–5714.PubMedGoogle Scholar
  34. Koopman P. and Cotton R. G. H. (1984) A factor produced by feeder cells which inhibits embryonal carcinoma cell differentiation characterization and partaial purification.Exp. Cell Res. 154, 233–242.PubMedGoogle Scholar
  35. Koufos A., Hansen M. F., Lampkin B. C., Workman N. L., Copeland N. G., Jenkins N. A., Cavenee W. K. (1984) Loss of alleles at loci on human chromosome 11 during genesis of Wilms’ tumor.Nature 309, 170–172.PubMedGoogle Scholar
  36. Knudson A. G. (1985) Hereditary cancer, oncogenes and antioncogenes.Cancer Res. 45, 1437–1443.PubMedGoogle Scholar
  37. Kurihara M., Tokunaga Y., Tsutsumi K., Kawaguchi T., Shigematsu K., Niwa M., and Mori K. (1989) Characterization of insulin like growth factor 1 and epidermal growth factor receptors in meningioma.J. Neurosurg. 71, 538–544.PubMedGoogle Scholar
  38. Lapeyre J. N. and Becker F. F. (1979) 5-methyl cytosine content of nuclear DNA during chemical hepatocarcinogenesis and in carcinomas which result.Biochem. Biophys. Res. Commun. 87, 698–705.PubMedGoogle Scholar
  39. Leff S. E., Rosenfeld M. G., and Evans R. M. (1986) Complex transcriptional units: Diversity in gene expression by alternative RNA processing.Annu. Rev. Biochem. 55, 1091–1117.PubMedGoogle Scholar
  40. Limon J., Rao U., Cin P. D., Gibas Z., and Sandberg A. A. (1986) Translocation (13;22) in a hemangiopericytoma.Cancer Genet. Cytogenet. 21, 309–318.PubMedGoogle Scholar
  41. Mapstone T., McMichael M., and Goldthwait D. (1991) Expression of platelet-derived growth factors, transforming growth factors, and the Ros gene in a variety of primary human brain tumors.Neurosurgery 28, 216–222.PubMedGoogle Scholar
  42. Maxwell M., Galanopoulous T., Hedley-Whyte E., Black P., and Antoniades H. (1990) Human meningiomas coexpress platelet derived growth factor (PDGF) and PDGF-receptor genes and their protein products.Int. J. Cancer. 46, 16–21.PubMedGoogle Scholar
  43. McKusick V. A. (1986) The gene map of homo sapiens: Status and prospectus.Cold Spring Harbor Symp. Quant. Biol. 51, 15–27.PubMedGoogle Scholar
  44. Metcalf D. and Gearing D. P. (1989) Fatal syndrome in mice engrafted with cells producing high levels of the leukemia inhibitory factor.Proc. Natl. Acad. Sci. USA 86, 5948–5952.PubMedGoogle Scholar
  45. Migeon B. R., Holland M. M., Driscoll D. J., and Robinson J. C. (1991) Programmed demethylation in CpG islands during human fetal development.Som. Cell Mol. Genet. 17, 159–168.Google Scholar
  46. Moreau J. F., Donaldson D. D., Bennet F., Witeck-Gianotti J., Clark S. C., and Wong G. G. (1988) Leukemia inhibitory factor is identical to the myeloid growth factor human interleukin for DA cells.Nature 336, 690–692.PubMedGoogle Scholar
  47. Mori M., Yamaguchi K., and Abe K. (1989) Purification of a lipoprotein lipase-inhibiting protein produced by a melanoma cell line associated with cancer cachiexia.Biochem. Biophys. Res. Commun. 160, 1085–1092.PubMedGoogle Scholar
  48. Murphy M., Reid K., Hilton D. J., and Bartlett P. F. (1991) Generation of sensory neurons is stimulated by leukemia inhibitory factor.Proc. Natl. Acad. Sci. USA 88, 3498–3501.PubMedGoogle Scholar
  49. Nakamura Y., Leppert M., O’Connell P., Wolff R., Holm T., Culver M., Martin C., Fujimoto E., Hoff M., Kumlin E., and White R. (1987) Variable number of tandem repeat (VNTR) markers for human gene mapping.Science 235, 1616–1622.PubMedGoogle Scholar
  50. Nawa H. and Sah D. W. Y. (1990) Different biological activities in conditioned media control the expression of a variety of neuropeptides in cultured sympathetic neurons.Neuron 4, 279–287.PubMedGoogle Scholar
  51. O’Connell P., Leach R., Cawthon R., Culver M., Stevens J., Viskichil D., Fournier R. E. K., Rich D., Ledbetter D., and White R. (1989) Two NF 1 translocation map within a 600 kilobase segment of 17q11.2.Science 244, 1087,1088.PubMedGoogle Scholar
  52. Okazaki M. and Takei S. I. (1989) Loss of genes on the long arm of chromosome 22 in human meningiomas.Mol. Biol. Med. 6, 251.Google Scholar
  53. Olson J., Beck D., Schlechte J., and Loh P. (1986) Hormonal manipulation of meningiomas in vitro.J. Neurosurg. 65, 99–107.PubMedGoogle Scholar
  54. Rathgen P. D., Toth S., Willis A., Heath J. K., and Smith A. G. (1990) Differentiation-inhibiting activity is produced in matrix-associated and diffusible forms that are generated by alternate promoter usage.Cell 62, 1105–1114.Google Scholar
  55. Rouleau G., Wertelecki W., Haines J. L., Hobbs W. J., Trofatter J. A., Seizinger B. R., Martuza R. L., Superneau D. W., Conneally P. M., and Gusella J. F. (1987) Genetic linkage of bilateral acoustic neurofibromastosis to a DNA marker on chromosome 22.Nature 329, 246–248.PubMedGoogle Scholar
  56. Rouleau G. A., Haines J. L., Bazanowski A., Collela-Crowley A., Trofatter J. A., Wexler N. S., Conneally P. M., and Gussela J. F. (1989) A genetic linkage map of the long arm of human chromosome 22.Genomics 4, 1–6.PubMedGoogle Scholar
  57. Rouleau G. A., Seizenger B. R., Wertelecki W., Haines J. L., Superneau D. W., Martuza R. L., and Gusella J. F. (1990) Flanking markers bracket the neurofibromatosis type 2 (NF2) gene on chromosome 22.Am. J. Human. Genet. 46, 323–328.Google Scholar
  58. Russell D. S. and Rubenstein L. J. (1989)Pathology of Tumors of the Nervous System, Edward Arnold, London, pp. 449–505.Google Scholar
  59. Sager R. (1989) Tumor suppressor genes: The puzzle and the promise.Science 246, 1406–1412.PubMedGoogle Scholar
  60. Saiki R. K., Scharf S., Fallona F., Mullis K. B., Horn G. T., Erlich H. A., and Arnheim N. A. (1985) Enzymatic amplification of β-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia.Science 230, 1350–1354.PubMedGoogle Scholar
  61. Seemayer T. A. and Cavenee W. K. (1989) Molecular mechanisms of oncogenesis.Lab. Invest. 60, 585–599.PubMedGoogle Scholar
  62. Seizinger B. R., Martuza R. L., and Gusella J. F. (1986) Loss of genes on chromosome 22 and tumorigenesis of human acoustic neuroma.Nature 322, 644–647.PubMedGoogle Scholar
  63. Seizinger B. R., Rouleau G. A., Ozelius L J., Lane A. H., Faryniarz A. G., Chao M. V., Huson S., Korf B. R., Parry D. M., Pericak-Vance M. A., Collins F. S., Hobbs W. J., Falcone B. G., Iannazzi J. S., Roy J. C., St. George-Hyslop P. H., Tanzi R. E., Bothwell M. A., Upadhyaya M., Harper P., Spence M. A., Mulvihill J. J. Aylsworth A. S., Vance J. M., Rossenwasser G. O. D., Gaskell P. C., Rosen A. D., Martuza R. L., Breakfield X. O., and Gusella J. F. (1987) Genetic linkage of Von Recklinghausen neurofibromatosis to the nerve growth factor receptor gene.Cell 49, 589–594.PubMedGoogle Scholar
  64. Seizinger B. R., Rouleau G., Ozelius L. J., Lane A. H., St George-Hyslop P., Huson S., Gusella J. F., and Martuza R. L. (1987a) Common pathogenetic mechanism for three tumor types in bilateral acoustic neurofibromatosis.Science 236, 317–319.PubMedGoogle Scholar
  65. Seizinger B. R., De La Monte S., Atkins L., Gusella J. F., and Martuza R. L. (1987b) Molecular genetic approach to human meningioma: Loss of genes on chromosome 22.Proc. Natl. Acad. Sci. USA 84, 5419–5423.PubMedGoogle Scholar
  66. Simpson R. J., Hilton D. J., Nice E. C., Rubira M. R., Metcalf D., Gearing D. P., Gough N. M., and Nicola N. A. (1988) Structural characterization of a murine myeloid leukemia inhibitory factor.Eur. J. Biochem. 175, 541–547.PubMedGoogle Scholar
  67. Smith A. G., Heath J. K., Donaldson D. D., Wong G. G., Moreau J., Stahl M., and Robers D. (1988) Inhibition of pluripotential embryonic stem cell differentiation by purified polypeptides.Nature 336, 688–690.PubMedGoogle Scholar
  68. Sutherland R., Baker E., Hyland V. J., Calan D. F., Stahl J., and Gough N. M. (1989) The gene for human leukemia inhibitory factor (LIF) maps to 22q12.Leukemia 3, 9–13.PubMedGoogle Scholar
  69. Takahashi J. A., Mori H., Fukumoto M., Igarashi I., Jaye M., Oda Y., Kikuchi H., and Hatanaka M. (1990) Gene expression of fibroblast growth factors in human gliomas and meningiomas: Demonstration of cellular source of basic fibroblast growth factor mRNA and peptide in tumor tissue.Proc. Natl. Acad. Sci. USA 87, 5710–5714.PubMedGoogle Scholar
  70. Tomida M., Yamamoto-Yamaguchi YH, and Hozumi M. (1984) Purification of a factor inducing differentiation of mouse myeloid leukemia M1 cells from conditioned medium of mouse fibroblast L929 cells.J. Biol. Chem. 259, 10,978–10,982.Google Scholar
  71. Trofatter J. A., MacCollin M. M., Rutter J. L., Murrell J. R., Duyao M. P., Parry D. M., Eldridge R., Kley N., Menon A. G., Pulaski K., Haase V. H., Ambrose C. M., Munroe D., Bove C., Haines J. L., Martuza R. L., MacDonald M. E., Seizinger B. R., Short M. P., Buckler A. J., and Gusella J. F. (1993) A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis Z tumor suppressor.Cell 72, 791–800.PubMedGoogle Scholar
  72. Viskochil D., Buchberg A. M., Xu G., Cawthon R. N., Stevens J., Wolff R. K., Culver M., Carey J. C., Copeland N. G., Jenkens N. A., White R., and O’Connell P. (1990) Deletion and a translocation interrupt a cloned gene at the neurofibromatosis type 1 locus.Cell 62, 187–192.PubMedGoogle Scholar
  73. Wertelecki W., Rouleau G. A., Superneau D. W., Forehand L. W., William J. P., Haines J. L., and Gusella J. F. (1988) Neurofibromatosis 2: Clinical and DNA linkage studies of a large kindred.N. Engl. J. Med. 319, 278–283.PubMedGoogle Scholar
  74. White R., Leppert M., Bishop D. T., Barker D., Berkowitz J., Brown C., Callahan P., Holm T., Jerominski L. (1985) Construction of linkage maps with DNA markers for human chromosomes.Nature 313, 101–105.PubMedGoogle Scholar
  75. Williams R. L., Hilton D. J., Pease S., Willson T. A., Stewart C. L., Gearing D. P., Wagner E. F., Metcalf D., Nicola N. A., and Gough N. M. (1988) Myeloid leukemia inhibitory factor maintains the developmental potential of embryonic stem cells.Nature 336, 684–687.PubMedGoogle Scholar
  76. Yamamori T., Fukada K., Aebersold R., Korsching S., Fann M., and Patterson P. H. (1989) A cholinergic neuronal differentiation factor from heart cells is identical to leukemia inhibitory factor.Science 246, 1412–1416.PubMedGoogle Scholar
  77. Zhang F. R., Dellatre O., Rouleau G., Couterier J., Lefrancois D., Thomas G., and Aurias A. (1990) The neuroepithelioma breakpoint on chromosome 22 is proximal to the meningioma locus.Genomics 6, 174–177.PubMedGoogle Scholar

Copyright information

© Humana Press Inc. 1994

Authors and Affiliations

  • Robert G. Pergolizzi
    • 1
  • Susan H. Erster
    • 2
  1. 1.Department of Pathology, Pediatrics, North Shore University HospitalCornell University Medical CollegeManhasset
  2. 2.Department of Research, North Shore University HospitalCornell University Medical CollegeManhasset

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