Summary
We have examined the genetic aberrations in two near-diploid glioblastoma multiforme cell lines that appear to have arisen from different glial lineages. One cell line, Hu-O-2A/Gb1, expresses antigens and metabolic profiles characteristic of the oligodendrocyte-type-2 astrocyte (0-2A) lineage of the rat central nervous system. This line generates, in vitro, cells with characteristics of 0-2A progenitor cells, oligodendrocytes and astrocytes. The second cell line, IN1434, is derived from an astrocyte or a precursor cell restricted to astrocytic differentiation. In Hu-O-2A/Gb1 the sole homologue of chromosome 10 is disrupted at band 10p11–12.1 by translocation with chromosomes X and 15. The translocation breakpoint is localized between genetic markers D10S2103 and [D10S637, D10S1962, D10S355]. Other aberrations include a 5;14 translocation, deletion of the long and short arms of chromosome 16 and loss of one copy of the CDKN2 gene. IN1434 cells share some cytogenetic abnormalities with Hu-O-2A/Gb1 cells, despite their apparent derivation from a different biological origin, but also have translocations involving the long and short arms of chromosome 1 and the long arm of chromosome 7, and deletion of chromosome 13 at bands 13q12–21.
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Amariglio, N., Friedman, E., Stiebel, O. M. H., Phelan, C., Collins, P., Nordenskjold, M., Brok-Simoni, F. & Rechavi, G. (1995). Analysis of microsatellite repeats in pediatric brain tumors. Cancer Genet Cytogenet 84: 56–59.
Barnett, S. C., Hutchins, A. M. & Noble, M. (1993). Purification of olfactory nerve ensheathing cells from the olfactory bulb. Dev Biol 155: 337–350.
Bignami, A., Eng, L. F., Dahl, D. & Uyeda, C. T. (1972). Localization of the glial fibrillary acidic protein in astrocytes by immunofluorescence. Brain Res 43: 429–435.
Bottenstein, J. E. & Sato, G. H. (1979). Growth of a rat neuroblastoma cell line in serum-free supplemented medium. Proc Natl Acad Sci USA 76: 514–517.
Chaplin, T., Ayton, P., Bernard, O. A., Saha, V., Della Valle, V., Hillion, J., Gregorini, A., Lillington, D., Berger, R. & Young, B. D. (1995). A novel class of zinc finger/leucine zipper genes identified from the molecular cloning of the t(10;11) translocation in acute leukemia. Blood 85: 1435–1441.
Debiec-Rychter, M., Alwasiak, J., Liberski, P. P., Nedoszytko, B., Babinska, M., Mrozek, K., Imielinski, B., Borowska-Lehman, J. & Limon J and Limon, J. (1995). Accumulation of chromosomal changes in human glioma progression. A cytogenetic study of 50 cases. Cancer Genet Cytogenet 85: 61–67.
Eisenbarth, G. S., Walsh, F. S. & Nirenberg, M. (1979). Monoclonal antibodies to a plasma membrane antigen of neurons. Proc Natl Acad Sci USA 76: 4913–4916.
Furnari, F. B., Huang, H-JS & Cavenee, W. K. (1995). Genetics and malignant progression in human brain tumors. Cancer Surveys 25: 233–275.
Gillaspy, G. E., Miller, R. H., Samols, D. & Goldthwait, D. A. (1993). Antigenic and differentiative heterogeneity among human glioblastomas. Cancer Lett 68: 215–224.
Gutowski, N., Bevan, K., Urenjak, J., Bhakoo, K., Williams, S., Gadian, D., Linskey, M., Engel, U., O’Leary, M., Blakemore, W. F., Mao, X., Sheer, D. & Noble, M. (1997). Isolation and characterization of a human oligodendrocyte-type-2 astrocyte (O-2A) progenitor cell glioblastoma, (in preparation)
Gyapay, G., Morissette, J., Vignal, A., Dib, C., Fizames, C., Millasseau, P., Marc, S., Bernardi, G., Lathrop, M. & Weissenbach, J. (1994). The 1993–94 Genethon human genetic linkage map. Nature Genetics 7: 246–339.
Hamilton, S. R., Liu, B., Parsons, R. E., Papadopoulos, N., Jen, J., Powell, S. M., Krush, A. J., Berk, T., Cohen, Z., Tetu, B., Burger, P. C., Wood, P. A., Taqi, F., Booker, S. V., Petersen, G. H., Offerhaus, G. J. A., Tersmette, A. C., Giardiello, F. M., Vogelstein, B. & Kinzler, K. W. (1995). The molecular basis of Turcots-syndrome. New Engl J Med 332: 839–847.
Ichimura, K., Schmidt, E. E., Miyakawa, A., Goike, H. M. & Collins, V. P. (1998). Distinct patterns of deletion on 10p and 10q suggest involvement of multiple tumor suppressor genes in the development of astrocytic gliomas of different malignancy grades. Genes Chrom Cancer 22: 9–15.
Jennemann, R., Rodden, A., Bauer, B. L., Mennel, H. D. & Wiegandt, H. (1990). Glycosphingolipids of human gliomas. Cancer Res 50: 7444–7449.
Johansson, B., Heim, S., Mandahl, N., Mertens, F. & Mitelman, F. (1993). Trisomy 7 in nonneoplastic cells. Genes Chrom Cancer 6: 199–205.
Kamb, A., Gruis, N. A., Weaver-Feldhaus, J., Liu, Q. Y., Karshman, K., Tavtigian, S. V., Stockert, E., Day, III R. S., Johnson, B. M. & Skolnick, M. H. (1994). A cell cycle regulator potentially involved in genesis of many tumor types. Science 264: 436–440.
Karlbom, A. E., James, C. D., Boethius, J., Cavenee, W. K., Collins, V. P., Nordenskjold, M. & Larsson, C. (1993). Loss of heterozygosity in malignant gliomas involves at least three distinct regions on chromosome 10. Hum Genet 92: 169–174.
Kashima, T., Tiu, S. N., Merrill, J. E., Vinters, H. V., Dawson, G. & Campagnoni, A. T. (1993). Expression of oligodendrocyte associated genes in cell lines derived from human gliomas and neuroblastomas. Cancer Res 53: 170–175.
Kim, D. H., Mohapatra, G., Bollen, A., Waldman, F. M. & Feuerstein, B. G. (1995). Chromosomal abnormalities in glioblastoma multiforme tumors and glioma cell lines detected by comparative genomic hybridisation. Int J Cancer 60: 812–819.
Kraus, J. A., Koopmann, J., Kaskel, P., Maintz, D., Brandner, S., Schramm, J., Louis, D. N., Wiestler, O. D. & Vondeimling, A. (1995). Shared allelic losses on chromosomes 1p and 19q suggest a common origin of oligodendroglioma and oligoastrocytoma. J Neuropath Exp Neurol 54: 91–95.
Li, J., Yen, C., Liaw, D., Podsypanina, K., Bose, B., Wang, S. I., Puc, J., Miliaresis, C., Rodgers, L., McCombie, R., Bigner, S. H., Giovanella, B. C., Ittmann, M., Tycko Hibshoosh, H., Wigler, M. H. & Parsons, R. (1997). PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast and prostate cancer. Science 275: 1943–1947.
Liu, B., Parsons, R., Papadopoulos, N., Nicolaides, N. C., Lynch, H. T., Watson, P., Jass, J. R., Dunlop, M., Wyllie, A., Peltomaki, P., de la Chapelle, A., Hamilton, S. R., Vogelstein, B. & Kinzler, K. W. (1996). Analysis of mismatch repair genes in hereditary non-polyposis colorectal cancer patients. Nature Med 2: 169–174.
Ma, NS-F, Zheng, C., Benchekroun, Y., Deaven, L. L., Longmire, J. L., Moir, D. T. & Mao, J. (1996). Characterization of a flow-sorted human chromosome 10 cosmid library by FISH. Cytogenet Cell Genet 74: 266–271.
Mao, X., Jones, T. A., Williamson, J., Gutowski, N. J., Pröschel, C., Noble, M. & Sheer, D. (1997). Assignment of the human and mouse LIM-kinase genes (LIMK1; Limk1) to chromosome bands 7q11.23 and 5G1, respectively, by in situ hybridisation. Cytogenet Cell Genet 74: 190–191.
Mitelman, F. (1994). Catalog of Chromosome Aberrations in Cancer 5th Edn, Wiley-Liss: New York
Mitelman, F. (ed) (1995). An International System for Human Cytogenetic Nomenclature, S. Karger: Basel
Mollenhauer, J., Siemann, S., Scheurlen, W., Korn, B., Hayashi, Y., Wilgenbus, K. K., von Deimling, A. & Poustka, A. (1997). DMBT1, a new member of the SRCR superfamily, on chromosome 10q25.3–26.1 is deleted in malignant brain tumours. Nature Genet 17: 32–39.
Noble, M. & Murray, K. (1984). Purified astrocytes promote the division of a bipotential glial progenitor cell. EMBO J 3: 2243–2247.
Noble, M., Fok-Seang, J. & Cohen, J. (1984). Glia are a unique substrate for the in vitro growth of CNS neurons. J Neurosci 4: 1892–1903.
Noble, M., Gutowski, N., Bevan, K., Engel, U., Linskey, M., Urenjak, J., Bhakoo, K. & Williams, S. (1995). From rodent glial precursor cell to human glial neoplasia in the oligodendrocyte-type-2 astrocyte lineage. Glia 15: 222–230.
Nobori, T., Miura, K., Wu, D. J., Lois, A., Takabayashi, K. & Carson, D. A. (1994). Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers. Nature 368: 753–756.
Proschel, C., Blouin, M. J., Gutowski, N. J., Ludwig, R. & Noble, M. (1995). Limk1 is predominantly expressed in neural tissues and phosphorylates serine, threonine and tyrosine residues in vitro. Oncogene 11: 1271–1281.
Raff, M. C., Miller, R. H. & Noble, M. (1983). A glial progenitor cell that develops in vitro into an astrocyte or an oligodendrocyte depending on the culture medium. Nature 303: 390–396.
Ranscht, B., Clapshaw, P. A., Price, J., Noble, M. & Seifert, W. (1982). Development of oligodendrocytes and Schwann cells studied with a monoclonal antibody against galactocerebroside. Proc Natl Acad Sci USA 79: 2709–2713.
Ritland, S. R., Ganju, V. & Jenkins, R. B. (1995). Region-specific loss of heterozygosity on chromosome 19 is related to the morphologic type of human glioma. Genes Chrom Cancer 12: 277–287.
Senger, G., Ragoussis, J., Trowsdale, J. & Sheer, D. (1993). Fine mapping of the human MHC class II region within chromosome band 6p21 and evalution of probe ordering using interphase fluorescence in situ hybridisation. Cytogenet Cell Genet 64: 49–53.
Schröck, E., Blume, C., Meffert, M-C, du Manoir, S., Bersch, W., Kiessling, M., Lozanowa, T., Thiel, G., Witkowski, R., Ried, T. & Cremer, T. (1996). Recurrent gain of chromosome arm 7q in low-grade astrocytic tumors studied by comparative genomic hybridisation. Genes Chrom Cancer 15: 199–205.
Singh, L. P., Pearl, D. K., Franklin, T. K., Sprin, P. M., Scheithauer, B. W., Coons, S. W., Johnson, P. C., Pfeiffer, S. E., Li, J., Knott, J. C. & Yates, A. J. (1994). Neutral glycolipid composition of primary human brain tumors. Mol Chem Neuropathol 21: 241–257.
Sommer, I. & Schachner, M. (1981). Monoclonal antibodies (O1 and O4) to oligodendrocyte cell surfaces: an immunocytological study in the central nervous system. Dev Biol 83: 311–327.
Steck, P. A., Pershouse, M. A., Jasser, S. A., Yung, W. K. A., Lin, H., Ligon, A. H., Langford, L. A., Baumgard, M. L., Hattier, T., Davis, T., Frye, C., Hu, R., Swedlund, B., Teng, D. H. F. & Tavtigian, S. V. (1997). Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nature Genet 15: 356–362.
Steinkasserer, A., Jones, T., Sheer, D., Koettnitz, K., Hauber, J. & Bevec, D. (1995). The eukaryotic co-factor for the human immunodeficiency virus type 1 (HIV-1) Rev protein, eIF-5A maps to chromosome 10q23.3. Three eIF-5A pseudogenes map to 10q23.3, 17q25 and 19q13.2. Genomics 25: 749–752.
Trybus, T. M., Burgess, A. C., Wojno, K. J., Glover, T. W. & Macoska, J. A. (1996). Distinct areas of allelic loss on chromosomal regions 10p and 10q in human prostate cancer. Cancer Res 56: 226–237.
Ueki, K., Ono, Y., Hensen, J. W., Efird, J. T., Vondeimling, A. & Louis, D. N. (1996). Cdkn2/p16 or Rb alterations occur in the majority of glioblastomas and are inversely correlated. Cancer Res 56: 150–153.
Van der Luijt, R. B., Khan, P. M., Vasen, H. F. A., Tops, C. M. J., van Leeuwen-Cornellise, I. S. J., Wijnen, J. T., van der Klift, H. M., Plug, R. J., Griffioen, G. & Fodde, R. (1997). Molecular analysis of the APC gene in 105 Dutch kindreds with familial adenomatous polyposis: 67 germline mutations identified by DGGE, PTT and southern analysis. Human Mutation 9: 7–16.
Zheng, C., Dorman, T. E., Wang, M. T., Braunschweiger, K., Schuster, M. K., Rothschild, C. B., Bowden, D. W., Torrey, D., Keith, T. P., Moir, D. T. & Mao, J. (1994). Generation of 124 sequence-tagged sites (STSs) and cytogenetic localization of 217 cosmids for human chromosome 10. Genomics 22: 55–67.
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Mao, X., Jones, T., Tomlinson, I. et al. Genetic aberrations in glioblastoma multiforme: translocation of chromosome 10 in an O-2A-like cell line. Br J Cancer 79, 724–731 (1999). https://doi.org/10.1038/sj.bjc.6690116
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DOI: https://doi.org/10.1038/sj.bjc.6690116
