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An Update on the Cellular and Molecular Biology of Brain Tumors

Published online by Cambridge University Press:  18 September 2015

Michael D. Cusimano*
Affiliation:
Division of Neuropathology, St. Michael's Hospital, 30 Bond Street, Toronto, Ontario, Canada M5B 1W8
*
Chief Resident, Division of Neurosurgery, St. Michael's Hospital, 30 Bond Street, Toronto, Ontario, Canada M5B 1W8
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Abstract:

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Patients with tumors of the central nervous system (CNS) remain difficult to treat despite recent advances in surgical, chemotherapeutic and radiotherapeutic techniques. A better understanding of the molecular and cellular biology of neoplasia is providing neuroscientists with a framework on which to devise novel therapies for these patients. It thus becomes imperative that neurologists and neurosurgeons be aware of these advances in basic science that may eventually have a positive impact on patient management. This paper reviews our present knowledge of the process of CNS oncogenesis and the roles that chemicals, viruses, oncogenes, growth inhibitor genes, and growth factors play in the process.

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Special Features
Copyright
Copyright © Canadian Neurological Sciences Federation 1989

References

REFERENCES

1.Farber, E.The multistep nature of cancer developments. Cancer Research 1984; 44: 42174223.Google Scholar
2.Shapiro, WR.Brain tumors. Seminars in oncology 1986; 16 (1): 13.Google Scholar
3.Althouse, R, Huff, J, Tomatis, L, et al. An evaluation of chemicals and industrial processes associated with cancer in humans based on human and animal data. IARC monographs vol. 1–20. Cancer Research 1980; 40: 112.Google Scholar
4.Kleihues, P, Bigner, DD.Tumors of the nervous system. In: Davison, AN, Thompson, RH (eds). Molecular Basis of Neuropathology. Edward Arnold Co, London 1981; 8796.Google Scholar
5.Walsh, JW, Zimmer, SG, Perdue, ML.Role of viruses in the induction of primary intracranial tumors. Neurosurgery 1982; 10 (5): 643662.CrossRefGoogle ScholarPubMed
6.Farewell, JR, Dohrmann, GJ, Marrett, LD, et al. Effect of SV40 virus-contaminated polio vaccine on the incidence and type of CNS neoplasms in children: A population-based study. Trans Am Neurol Assoc 1979; 104: 261263.Google Scholar
7.Heinonen, OP, Shapiro, S, Monson, RR, et al. Immunization during pregnancy against poliomyelitis and influenza in relation to childhood malignancy. Int J Epidermiol 1973; 2: 229235.CrossRefGoogle ScholarPubMed
8.Geissler, E, Schemeck, S, Waehite, H, et al. Further studies on the relationship of SV40-like viruses to human tumors. Cold Spring Harbor Conf Cell Proliferation 1980; 7: 343356.Google Scholar
9.Israel, MA, Martin, MA, Takemoto, KK, et al. Evaluation of normal and neoplastic human tissue for BK virus. Virology 1978; 90: 187196.CrossRefGoogle ScholarPubMed
10.Ibelgaufts, H.Are human DNA tumor viruses involved in the pathogenesis of human neurogenic tumors? Neurosurg Rev 1982; 4: 324.CrossRefGoogle Scholar
11.Ibelgaufts, H.DNA viruses and brain tumors TINS 1982; 5: 1620.Google Scholar
12.Takenaka, N, Mikoshiba, K, Takamatsu, K, et al. Immunohistochemical detection of the gene product of Rous sarcoma virus in human brain tumors. Brain Res 1985; 337: 201207.CrossRefGoogle ScholarPubMed
13.Takemoto, KK, Rabson, AS, Mullarbey, MF, et al. Isolation of papovavirus from brain tumor and urine of a patient with Wiskott- Aldrich syndrome. J Natl Cancer Inst 1974; 53: 12051207.CrossRefGoogle ScholarPubMed
14.Scherneck, S, Rudolph, M, Geissler, E, et al. Isolation of an SV-40 like papovavirus from a human glioblastoma. Int J Cancer 1979; 24: 523531.CrossRefGoogle Scholar
15.Schmidek, HH.The molecular genetics of nervous system tumor J Neurosurg 1987; 67: 116.CrossRefGoogle Scholar
16.Palmiter, RD, Brinster, RL.Transgenic mice Cell 1985; 41: 343345.CrossRefGoogle ScholarPubMed
17.Bigner, DD, Pegram, CN.Virus induced experimental brain tumors and putative associations of viruses with human brain tumors: a review. In: Thompson, RA, Green, JR eds. Advances in Neurology. Raven Press, New York 1976; 15: 5783.Google ScholarPubMed
18.Saris, SC, Bigner, DD.Experimental Neuro-oncology. In: Crockard, D, Thomas, BK eds. Neurosurgery: The scientific basis of clinical medicine. St. Louis, Mosby 1985; 392416.Google Scholar
19.Walker, JS, Bigner, DD.Virus induced brain tumors. In: Wilkins, RH, Rengachary, S, eds. Neurosurgery. McGraw Hill Book Co, New York 1985; 522525.Google Scholar
20.Seligman, AM, Shear, MJ.Studies in carcinogenesis VIII. Experimental production of brain tumors in mice with methylcholanthrene. Am J Cancer 1939; 37: 364399.Google Scholar
21.Lantos, PL.Development of nitrosurea-induced brain tumors — with special note on changes occurring during latency. Food Chem Toxicol 1986; 24 (2): 121127.CrossRefGoogle ScholarPubMed
22.Hodgson, RM, Weissler, M, Kleihues, P.Preferential methylation of target organ DNA by the esophageal carcinogen N-nitrosomethylbenzylamine. Carcinogenesis 1980; 1: 861866.CrossRefGoogle Scholar
23.Kleihues, P, Buechleler, J.Long term persistence of O6-methylguanine in rat brain DNA. Nature 1977; 269: 625626.CrossRefGoogle ScholarPubMed
24.Kleihues, P, Bamborschke, S, Doerjes, G.Persistence of alkylated DNA bases in the Mongolian gerbil (Meriones ungiuiculates) following a single dose of methylnitrosurea. Carcinogenesis 1980; 1: 111113.CrossRefGoogle Scholar
24.Kleihues, P, Bamborschke, S, Doerjes, G.Persistence of alkylated DNA bases in the Mongolian gerbil (Meriones ungiuiculates) following a single dose of methylnitrosurea. Carcinogenesis 1980; 1: 111113.CrossRefGoogle Scholar
25.Lloyd, HM, Meares, JD, Jacob, J.Effects of estrogen and bromocryptine on in vivo secretion and mitosis in prolactin cells. Nature 1975; 225: 497498.CrossRefGoogle Scholar
26.Asa, SL, Kovacs, K, Tindall, GE, et al. Cushing’s disease associated with an intrasellar gangliocytoma producing corticotropinreleasing factor. Ann Int 1984; 101: 789793.CrossRefGoogle Scholar
27.Billestrup, N, Swanson, LW, Vale, W.Growth hormone-releasing factor stimulates proliferation of somatotrophs in vitro. Proc Natl Acad Sci, USA 1986; 83: 68546857.CrossRefGoogle ScholarPubMed
28.Bordi, C, Plato, F, Cartagna, G, et al. Argyophil cell hyperplasia of fundic mucosa in patients with chronic atrophic gastritis. Digestion 1986; 36: 130143 (Suppl 1).CrossRefGoogle Scholar
29.Borch, K, Renvall, H, Leedberg, G.Gastric endocrine cell hyperplasia with carcinoid tumors in pernicious anemia. Gastroenterology 1985; 88: 638648.CrossRefGoogle ScholarPubMed
30.Carey, RM, Varma, SK, Drake, CR Jr, et al. Ectopic secretion of corticotrophin-releasing factor as a cause of Cushing’s syndrome: a clinical, morphological and biochemical study. N Engl J Med 1984; 311: 13120.CrossRefGoogle ScholarPubMed
31.Kovacs, K, Horvath, E, Ilse, G.Ultrastructure of the human thyrotroph in TSH excess. Proc XI Int Cong on Electron Microscopy. Kyoto 1986; 30253026.Google Scholar
32.Nelson, DH, Meakin, JW, Thorn, GW.ACTH-producing pituitary tumors following adrenalectomy for Cushing’s syndrome. Ann Intern Med 1960; 52: 560569.Google ScholarPubMed
33.Pawlikowski, M.The link between secretion and mitosis in the endocrine glands. Life Sciences 1982; 30: 315320.CrossRefGoogle ScholarPubMed
34.Chiodini, DG, Liuzzi, A, Verde, G, et al. Size reduction of a prolactin secreting adenoma during long-term treatment with dopamine agonist lisuride. Clin Endocrinol 1980; 12: 4751.CrossRefGoogle ScholarPubMed
35.McGregor, AM, Scanlon, MF, Hall, R, et al. Effects of bromocryptine on pituitary tumor size. Br Med J 1979; 2: 700703.CrossRefGoogle Scholar
36.Kovacs, K, Horvath, E.Tumors of the pituitary gland. Atlas of Tumor Pathology Fascicle 21. Armed Forces Institute of Pathology, Washington, DC 1986; 107108.Google Scholar
37.Land, H, Parada, LF, Weinberg, RA.Cellular oncogenes and multistep carcinogenesis. Science 1983; 298: 343347.Google Scholar
38.Payne, GS, Bishop, JM, Varmus, HE.Multiple arrangements of viral DNA and an activated host oncogene in bursal lymphomas. Nature 1982; 295: 209214.CrossRefGoogle Scholar
39.Der, CJ.Cellular oncogenes and human carcinogenesis. Clin Chem 1987; 33 (5): 641646.CrossRefGoogle ScholarPubMed
40.Gilbert, F.Chromosomes, genes and cancer: A classification of chromosome abnormalities in cancer. J Natl Cancer Inst 1983; 71: 107114.Google Scholar
41.Balaban, G, Gilbert, F, Nichols, W, et al. Abnormalities of chromosome 13 in retinoblastomas from individuals with normal consitutional karyotypes. Cancer Genet Cytogenet 1982; 6: 213221.CrossRefGoogle Scholar
42.Gilbert, F, Feder, M, Balaban, G, et al. Human neuroblastomas and abnormalities of chromosomes 1 and 17. Cancer Res 1984; 44: 54445449.Google ScholarPubMed
43.Riccardi, VM, Sujansky, E, Smith, AC, et al. Chromosomal imbalance in Aniridia-Welm’s tumor association. Pediatrics 1978; 61: 604610.CrossRefGoogle ScholarPubMed
44.Murray, MJ, Cunningham, JM, Parada, LF, et al. The HL-60 transforming sequence: A ras oncogene coexisting with altered myc genes in hematopoietic tumors. Cell 1983; 33: 749757.CrossRefGoogle ScholarPubMed
45.Assoian, RK, Grotendorst, GR, Miller, DM.Cellular transformation by coordinated action of three peptide growth factors from human platelets. Nature 1984; 309: 804806.CrossRefGoogle ScholarPubMed
46.Cooper, GM, Neiman, PE.Two distinct candidate transforming genes of lymphoid leukosis virus-induced neoplasms. Nature 1981; 292: 857858.CrossRefGoogle ScholarPubMed
47.Land, H, Parada, LF, Weinberg, RA.Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes. Nature 1983; 304: 596602.CrossRefGoogle ScholarPubMed
48.Eliyahu, D, Raz, A, Gruss, P, et al. Participation of p53 cellular tumor antigen in transformation of normal embryonic cells. Nature 1984; 312: 646649.CrossRefGoogle ScholarPubMed
49.Parada, LF, Land, H, Weinberg, RA, et al. Cooperation between gene encoding p53 tumor antigen and ras in cellular transformation. Nature 1984; 312: 649651.CrossRefGoogle Scholar
50.Jenkins, JR.Rudge, K, Currie, GA.Cellular immortalization by a cDNA clone encoding the transformation-associated phosphoprotein p53. Nature 1984; 312: 651654.CrossRefGoogle ScholarPubMed
51.Ruley, HE.Adenovirus early region 1A enables viral and cellular transforming genes to transform primary cells in culture. Nature 1983; 304: 602606.CrossRefGoogle ScholarPubMed
52.Weinstein, IB.Growth factors, oncogenes and multistage carcinogenesis. J Cell Biochem 1987; 33: 213224.CrossRefGoogle ScholarPubMed
53.Westermark, B, Nister, M, Heldin, CH.Growth factors and oncogenes in human malignant glioma. Neurologic Clin 1985; 3 (4): 785799.CrossRefGoogle ScholarPubMed
54.Ashall, F, Puck, TT.Cytoskeletal involvement in CAMP-induced sensitization of chromatin to nuclease digestion in transformed Chineere hamster ovary Kl cells. Proc Natl Acad Sci USA 1984; 81: 51455149.CrossRefGoogle Scholar
55.Sisskin, E, Weinstein, IB.Isolation and characterization of a morphologic variant of Chineese hamster (CHO) cells. J Cell Physiol 1980; 102 (2): 141153.CrossRefGoogle Scholar
56.Niskizuka, YPerspectives on the role of protein kinase C in stimulus- response coupling. J Natl Cancer Inst 1986; 76: 363370.Google Scholar
57.Niskizuka, YThe role of protein kinase C in cell surface signal transduction and tumor promotion. Nature 1984; 308: 693698.CrossRefGoogle Scholar
58.Berridge, MJ, Irvine, RF.Inositol Triphosphate. A novel second Messenger in Signal Transduction. Nature 1984; 312: 315321.CrossRefGoogle Scholar
59.Kelly, K, Cochran, BH, Stiles, CD, et al. Cell specific regulation of the c-myc gene by lymphocyte mitogens and platelet-derived growth factor. Cell 1983; 35: 603610.CrossRefGoogle ScholarPubMed
60.Kruijer, W, Cooper, JA, Hunter, T, et al. Platelet derived growth factor induced rapid but transient expression of the c-fos gene and protein. Nature 1984; 312: 711716.CrossRefGoogle ScholarPubMed
61.Muller, R, Bravo, R, Burckhardt, J.Induction of c-fos gene and protein by growth factors precedes activation of c-myc. Nature 1984; 312: 716720.CrossRefGoogle ScholarPubMed
62.Shapiro, JR, Pu, PY, Mohamed, AN, et al. Regional heterogeneity in high grade gliomas. Proc Amer Assn Cancer Res 1984; 25: 375382.Google Scholar
63.Heldin, C-H, Westermark, B, Wasteson, A.Specific receptors for platelet-derived growth factor on cells derived from connective tissue and glia. Proc Natl Acad Sci USA 1981; 78: 36643668.CrossRefGoogle ScholarPubMed
64.Simpson, DL, Morrison, R, de Vellis, J, et al. Epidermal growth factor binding and mitogenic activity on purified populations of cells from the central nervous system. J Neurosci Res 1962; 8: 453462.CrossRefGoogle Scholar
65.Heldin, C-H, Westermark, B, Wasteson, A.Chemical and biological properties of growth factor from human-cultured osteosarcoma cells: Resemblance with platelet-derived growth factor. J Cell Physiol 1980; 105: 235246.CrossRefGoogle ScholarPubMed
66.Graves, DT, Owen, AJ, Antoniades, HN.Evidence that a human osteosarcoma cell line which secretes a mitogen similar to platelet-derived growth factor requires growth factors present in platelet-poor plasma. Cancer Res 1983; 43: 8387.Google ScholarPubMed
67.Betsholtz, C, Heldin, C-H, Nister, M, et al. Synthesis of a PDGF-like growth factor in human glioma and sarcoma cells suggests the expression of the cellular homologue to the transforming protein of simian sarcoma virus. Biochem Biophys Res Commun 1983; 117: 176182.CrossRefGoogle Scholar
68.Nister, M, Heldin, C-H, Wasteson, A, et al. A platelet-derived growth factor analog produced by a human clonal glioma cell line. Ann NY Acad Sci 1982; 397: 2533.CrossRefGoogle ScholarPubMed
69.Dalla-Favera, RC, Gallo, RC, Giallongo, A, et al. Chromosomal localization of the human homolog (c-sis) of the simian sarcoma virus one gene. Science 1982; 218: 686688.CrossRefGoogle Scholar
70.Swan, DC, McBride, OW, Robbins, KC, et al. Chromosomal mapping of the simian sarcoma virus one gene analogue in human cells. Proc Natl Acad Sci USA 1982; 79: 46914695.CrossRefGoogle Scholar
71.Davies, RL, Grosse, VA, Kucherlapati, R, et al. Genetic analysis of epidermal growth factor action: Assignment of human epidermal growth factor receptor gene to chromosome 7. Proc Natl Acad Sci USA 1980; 77: 41884192.CrossRefGoogle ScholarPubMed
72.Shimizu, N, Kondo, I, Gamou, S, et al. Genetic analysis of hyperproduction of epidermal growth factor receptors in human epidermoid carcinoma A431 cells. Somatic Cell Mol Genet 1984; 10: 4553.CrossRefGoogle ScholarPubMed
73.Waterfield, MD, Scrace, GT, Whittle, N, et al. Platelet-derived growth factor is structurally related to the putative transforming protein p28 sis of simian sarcoma virus. Nature 1983; 304: 3539.CrossRefGoogle Scholar
74.Robbins, KC, Antoniades, HN, Sushilkumar, G, et al. Structural and immunological similarities between simian sarcoma virus gene product(s) and human platelet-derived growth factor. Nature 1983; 305: 605608.CrossRefGoogle ScholarPubMed
75.Betsholtz, C, Westermark, B, Ek, B, et al. Coexpression of a PDGFlike growth factor and PDGF receptors in a human osteosarcoma cell line. Implications for autocrine receptor activation. Cell 1984; 39: 447457.CrossRefGoogle Scholar
76.Hunter, T.The epidermal growth factor receptor gene and its product. Nature 1984; 307: 521527.Google Scholar
77.Downward, J, Yarden, Y, Mayes, E, et al. Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences. Nature 1984; 307: 521527.CrossRefGoogle ScholarPubMed
78.Libermann, TA, Razon, N, Bartal, AD, et al. Expression of epidermal growth factor receptors in human brain tumors. Cancer Res 1984; 44: 753760.Google ScholarPubMed
79.Libermann, TA.Nusbaum, HR, Razon, N, et al. Amplification, enhanced expression and possible rearrangement of the EGF receptor gene in primary human brain tumors of glial origin. Nature 1984; 313: 144147.CrossRefGoogle Scholar
80.Todaro, GT, Marquardt, H, Twardzik, DR, et al. Transforming growth factors produced by tumor cells. In: Owens, AHCoffey, DS, Baylin, SB, eds: Tumor Cell Heterogeneity: Origin and Implications Orlando, Fla, Academic 1982; 205224.Google Scholar
81.Stromberg, K, Hudgins, WR, Dormann, LS, et al. Human brain tumor-associated urinary high molecular weight transforming growth factor: A high molecular weight form of epidermal growth factor. Cancer Res 1987; 47: 11901196.Google ScholarPubMed
82.Schwab, M, Alitalo, K, Klempnauer, K-H, et al. Amplified DNA with limited homology to myc cellular oncogene is shared by human neuroblastoma cell lines and a neuroblastoma tumor. Nature (London) 1983; 305: 245248.CrossRefGoogle Scholar
83.Kohl, NE, Kanda, N, Schreck, RR, et al. Transposition and amplification of oncogene-related sequences in human neuroblastomas. Cell 1983; 35: 359367.CrossRefGoogle ScholarPubMed
84.Seeger, RC, Brodeur, GM, Sather, H, et al. Association of multiple copies of the N-myc oncogene with rapid progression of neuroblastomas. N Engl J Med 1985; 313: 11111116.CrossRefGoogle ScholarPubMed
85.Schecter, AL, Hung, MC, Vaidyanathan, L, et al. The neu gene: an erb-B-homologous gene distinct from and unlinked to the gene encoding the EGF receptor. Science 1985; 229: 976978.CrossRefGoogle Scholar
86.Sachs, L.Growth, differentiation and the reversal of malignancy. Sci Am 1986; 354 (1): 4047.CrossRefGoogle Scholar
87.Cavenee, WK, Hansen, MF, Norderskjold, M, et al. Science 1985; 228: 501503.CrossRefGoogle Scholar
88.Koufos, A, Hansen, MF, Lamphin, BC, et al. Loss of alleles at loci on human chromosome 11 during genesis of Wilms’ tumor. Nature 1984; 309: 170172.CrossRefGoogle Scholar
89.Green, AR, Wyke, JA.Anti-oncogenes. A subset of regulatory genes involved in carcinogenesis?. Lancet 1985; 2: 475477.CrossRefGoogle ScholarPubMed
90.Sager, R.Genetic suppression of tumor formation: A new frontier in cancer research. Cancer Res 1986; 46: 15731580.Google ScholarPubMed
91.Gateff, E.Cancer, genes, and development: the Drosophila case. Adv Cancer Res 1982; 37: 3374.CrossRefGoogle ScholarPubMed
92.Rubinstein, LJ.Tumors of the Central Nervous System. Second Series Fascicle 6. Armed Forces Institute of Pathology 1985; 154157.Google Scholar
93.Freshney, RI.Induction of differentiation in neoplastic cells. Anticancer Res 1985; 5: 111130.Google ScholarPubMed
94.Seeger, RC.Neuroblastoma: Clinical perspectives, monoclonal antibodies, and retinoic acid. Ann Int Med 1982; 97: 873884.CrossRefGoogle ScholarPubMed
95.Bast, RCPrinciples of Cancer Biology: Tumor Immunology. In: DeVita, VTHellman, S, Rosenberg, S, eds. Cancer Principles and Practice of Oncology JB Lipincott Co, Philadelphia 1986; 1 (2): 125150.Google Scholar
96.Bunge, RP, Waksman, BH.Glial development and interactions. TINS 1985; 8: 424427.Google Scholar
97.Suzuki, N, Kanno, T, Nagata, Y, et al. Inhibition of proliferative growth in glioma cells by calmodulin antagonists. J Neurosurg 1986; 65: 7479.CrossRefGoogle ScholarPubMed
98.Whitfield, JF, Boynton, JP, Mac Manus, RH, et al. The roles of calcium and cyclic AMP in cell proliferation. Ann NY Acad Sci 1980; 339: 216240.CrossRefGoogle ScholarPubMed
99.Rutka, JT.Effects of extracellular matrix proteins on the growth and differentiation of an anaplastic glioma cell line. Can J Neurol Sci 1986; 13: 301306.CrossRefGoogle ScholarPubMed