Molecular Mechanisms of Oncogenesis

  • Thomas A. Seemayer
  • Webster K. Cavenee

Abstract

A review of the literature of the past several years shows hundreds of reports describing oncogene identification, expression, deregulation, amplification and mutation, chromosomal alterations and molecular events in experimental and naturally occurring cancer. It is our intention here to focus on concepts and principles and to present an overview of the molecular events thought to be important in cancer. We discuss the history and nature of oncogenes and then consider cytogenetic and molecular mechanisms which may be operative in neoplasia. Because many contributions originate from analyses of relatively rare pediatric cancers, particular emphasis will be accorded cancers arising in children. Since the molecular events uncovered in the childhood cancers appear to be operative in adults, we will consider a few of these diseases as well.

Keywords

Codon Adenocarcinoma Adenoma Folic Acid Catalase 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Adams JM, Harris AW, Pinkert CA, Corcoran LM, Alexander WS, Cory S, Palmiter RD, Brinster RL: The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice. Nature (London) 318:533, 1985Google Scholar
  2. 2.
    Ali IU, Campbell G, Lidereau R, Callahan R: Amplification of c-erbB-2 and aggressive human breast tumors? Science 240:1795, 1988Google Scholar
  3. 3.
    Ali IU, Lidereau R, Theillet C, Callahan R: Reduction to homozygosity of genes on chromosome 11 in human breast neoplasia. Science 238:185, 1987PubMedGoogle Scholar
  4. 4.
    Almoguera C, Shibata D, Forrester K, Martin J, Arnheim N, Perucho M: Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell 53:549, 1988PubMedGoogle Scholar
  5. 5.
    Andersen SR, Geertinger P, Larsen HW, Mikkelsen MN, Parbing A, Vestermark S, Warburg M: Aniridia, cataract and gonadoblastoma in a mentally retarded girl with deletion of chromosome 11. Ophthalmologia 176:171, 1978Google Scholar
  6. 6.
    Aurias A, Rimbaut C, Buffe D, Dubousset J, Mazabraud A. Chromosomal translocations in Ewing’s sarcoma. N Engl J Med 309:496, 1983Google Scholar
  7. 7.
    Avery OT, MacLeod CM, MacCarty A: Studies on the chemical nature of the substances inducing transformation of pneumococcal types. J Exp Med 79:133, 1944Google Scholar
  8. 8.
    Balaban G, Gilbert F, Michols W, Meadows AT, Shields J: Abnormalities of chromosome 13 in retinoblastomas from individuals with normal constitutional karyotypes. Cancer Genet Cytogenet 6:213, 1982PubMedGoogle Scholar
  9. 9.
    Baltimore D: RNA-dependent DNA polymerase in virions of RNA tumor viruses. Nature (London) 226:1209, 1970Google Scholar
  10. 10.
    Barker D, Wright E, Nguyen K, Cannon L, Fain P, Goldgar D, Bishop DT, Carey J, Baty B, Kivlin J, Willard H, Waye JS, Greig G, Leinwand L, Nakamura Y, O’Connell P, Leppert M, Lalouel J-M, White R, Skolnick M: Gene for von Recklinghausen neurofibromatosis is in the pericentromeric region of chromosome 17. Science 236:1100, 1987PubMedGoogle Scholar
  11. 11.
    Barker PE: Double minutes in human tumor cells. Cancer Genet Cytogenet 5:81, 1982PubMedGoogle Scholar
  12. 12.
    Beckwith JB: Macroglossia, omphalocele, adrenal cytomegaly, gigantism, and hyperplastic visceromegaly. Birth Defects Series V, pp 188–196. New York, National Foundation-March of Dimes, 1969Google Scholar
  13. 13.
    Ben-Neriah Y, Daley GQ, Mes-Masson AM, Witte ON, Baltimore D: The chronic myelogenous leukemia-specific p210 protein is the product of the bcr/abl hybrid gene. Science 233:212, 1986PubMedGoogle Scholar
  14. 14.
    Bernards R, Dessain SK, Weinberg RA: N-myc amplification causes down-modulation of MHC Class I antigen expression in neuroblastoma. Cell 47:667, 1986PubMedGoogle Scholar
  15. 15.
    Bishop JM: Oncogenes. Sci Am 246:80, 1982PubMedGoogle Scholar
  16. 16.
    Bishop JM: Viral oncogenes. Cell 42:23, 1985PubMedGoogle Scholar
  17. 17.
    Bishop JM: The molecular genetics of cancer. Science 235:305, 1987PubMedGoogle Scholar
  18. 18.
    Bodmer WF, Bailey CJ, Bodmer J, Bussey HJR, Ellis A, Gorman P, Lucibello FC, Murday VA, Rider SH, Scambler P, Sheer D, Solomon E, Spurr NK: Localization of the gene for familial adenomatous polyposis on chromosome 5. Nature (London) 328:614, 1987Google Scholar
  19. 19.
    Bogenmann E, Locherie MA, Simon MI: Cone cell-specific genes expressed in retinoblastoma. Science 240:76, 1988PubMedGoogle Scholar
  20. 20.
    Bos JL, Fearon ER, Hamilton SR, Verlaan-de Vries M, van Boom JH, van der Eb AJ, Vogelstein B: Prevalence of ras gene mutations in human colorectal cancers. Nature (London) 327:293, 1987Google Scholar
  21. 21.
    Boveri T: Zur Frage der Entstehung Malinger Tumoren. Jena, Germany, Fisher, 1914Google Scholar
  22. 22.
    Brauch H, Johnson B, Hovis J, Yano T, Gazdar A, Pettengill OS, Graziano S, Sorenson GD, Poiesz BJ, Minna J, Linehan M, Zbar B: Molecular analysis of the short arm of chromosome 3 in small-cell and non-small-cell carcinoma of the lung. N Engl J Med 317:1109, 1987PubMedGoogle Scholar
  23. 23.
    Brissenden JE, Ullrich A, Francke U: Human chromosomal mapping of genes for insulin-like growth factors I and II and epidermal growth factor. Nature (London) 310:781, 1984Google Scholar
  24. 24.
    Brodeur GM, Seeger RC, Schwab M, Varmus HE, Bishop MJ: Amplification of N-myc in untreated human neuroblastomas correlates with advanced disease stage. Science 224:1121, 1984PubMedGoogle Scholar
  25. 25.
    Brugge JS, Eirkson RL: Identification of a transformation-specific antigen induced by an avian sarcoma virus. Nature (London) 269:346, 1977Google Scholar
  26. 26.
    Capon DJ, Chen EY, Levinson AD, Seeburg PH, Goeddel DV: Complete nucleotide sequences of the T24 human bladder carcinoma oncogene and its normal homologue. Nature (London) 302:33, 1982Google Scholar
  27. 27.
    Cavenee WK, Dryja TP, Phillips RA, Benedict WF, Godbout R, Gallie BL, Murphree AL, Strong LC, White RL: Expression of recessive alleles by chromosomal mechanisms in retinoblastoma. Nature (London) 305:779, 1983Google Scholar
  28. 28.
    Cavenee WK, Hansen MF, Nordenskjold M., Kock E, Maumenee I, Squire JA, Phillips RA, Gallie BL: Genetic origin of mutations predisposing to retinoblastoma. Science 228:501, 1985PubMedGoogle Scholar
  29. 29.
    Cavenee WK, Murphree AL, Shull MM, Benedict WF, Sparkes RS, Kock E, Nordenskjold M: Prediction of familial predisposition to retinoblastoma. N Engl J Med 314:1201, 1986PubMedGoogle Scholar
  30. 30.
    Chan LC, Karhi KK, Rayter SI, Heisterkamp N, Eridani S, Powles R, Lawler SD, Groffen J, Foulkes JG, Greaves MF, Wiedemann LM: A novel abl protein expressed in Philadelphia chromosome positive acute lymphoblastic leukaemia. Nature (London) 325:635, 1987Google Scholar
  31. 31.
    Cleary ML, Galili N, Sklar J: Detection of a second t(14;18) breakpoint cluster region in human follicular lymphomas. J Exp Med 164:315, 1986PubMedGoogle Scholar
  32. 32.
    Cleary ML: Oncogenes and translocations in the pathogenesis of T-cell neoplasia. Am J Surg Pathol 12:163, 1988Google Scholar
  33. 33.
    Cohen AJ, Li FP, Berg S, Marchetto DJ, Tsai S, Jacobs SC, Brown RS: Hereditary renal-cell carcinoma associated with a chromosomal translocation. N Engl J Med 301:592, 1979PubMedGoogle Scholar
  34. 34.
    Comings DE: A general theory of carcinogenesis. Proc Natl Acad Sci USA 70:3324, 1973PubMedGoogle Scholar
  35. 35.
    Croce CM, Tsujimoto Y, Erikson J, Nowell PC: Chromosomal translocations and B cell neoplasia. Lab Invest 51:258, 1984PubMedGoogle Scholar
  36. 36.
    Daley GQ, McLaughlin J, Witte ON, Baltimore D: The CML-specific p210 bcr/abl protein, unlike v-abl, does not transform NIH/3T3 fibroblasts. Science 237:532, 1987PubMedGoogle Scholar
  37. 37.
    Dalla-Favera R, Bregni M, Erikson J, Patterson D, Gallo RC, Croce CM: Human c-myc onc gene is located on the region of chromosome 8 that is translocated in Burkitt lymphoma cells. Proc Natl Acad Sci USA 79:7824, 1982PubMedGoogle Scholar
  38. 38.
    Davis LM, Stallard R, Thomas GH, Couillin P, Junien C, Nowak NJ, Shows TB: Two anonymous DNA segments distinguish the Wilms’ tumor and aniridia loci. Science 241:840, 1988PubMedGoogle Scholar
  39. 39.
    DeCaprio JA, Ludlow JW, Figge J, Shew J-Y, Huang C-M, Lee W-H, Marsilo E, Paucha R, Livingston DM: SV40 large tumor antigen forms a specific complex with the product of the retinoblastoma susceptibility gene. Cell 54:275, 1988PubMedGoogle Scholar
  40. 40.
    Doolittle RF, Hunkapiller MW, Hood LE, Devare SG, Robbins KC, Aaronson SA, Antoniades HN: Simian sarcoma virus onc gene, v-sis, is derived from the gene encoding a platelet-derived growth factor. Science 221:275, 1983PubMedGoogle Scholar
  41. 41.
    Downward J, Yarden Y, Mayes E, Scrace G, Totty N, Stockwell P, Ullrich A, Schlessinger J, Waterfield MD: Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences. Nature (London) 307:521, 1984Google Scholar
  42. 42.
    Dreazen O, Rassool F, Sparkes RS, Klisak I, Goldman JM, Gale RP: Do oncogenes determine clinical features in chronic myeloid leukaemia? Lancet 1:402, 1987Google Scholar
  43. 43.
    Dryja TP, Rapaport JM, Joyce JM, Petersen RA: Molecular detection of deletions involving band ql4 of chromosome 13 in retinoblastomas. Proc Natl Acad Sci USA 83:7391, 1986PubMedGoogle Scholar
  44. 44.
    Dubeau L, Chandler LA, Gralow JR, Nichols PW, Jones PA: Southern blot analysis of DNA extracted from formalin-fixed pathology specimens. Cancer Res 46:2694, 1986Google Scholar
  45. 45.
    Dunn JM, Phillips RA, Becker AJ, Gallie BL: Identification of germline and somatic mutations affecting the retinoblastoma gene. Science 241:1797, 1988PubMedGoogle Scholar
  46. 46.
    Egan SE, Wright JA, Jarolim L, Yanagihara K, Bassin RH, Greenberg AH: Transformation by oncogenes encoding protein kinases induces the metastatic phenotype. Science 238:202, 1987PubMedGoogle Scholar
  47. 47.
    Fearon ER, Vogelstein B, Feinberg AP: Somatic deletion and duplication of genes on chromosome 11 in Wilms’ tumor. Nature (London) 309:176, 1984Google Scholar
  48. 48.
    Fearon ER, Feinberg AP, Hamilton SH, Vogelstein B: Loss of genes on the short arm of chromosome 11 in bladder cancer. Nature (London) 318:377, 1985Google Scholar
  49. 49.
    Fearon ER, Hamilton SR, Vogelstein B: Clonal analysis human colorectal tumors. Science 238:193, 1987PubMedGoogle Scholar
  50. 50.
    Feinberg AP, Vogelstein B, Droller MJ, Baylin SB, Nelkin BD: Mutation affecting the 12th amino acid of the c-Ha-ras oncogene product occurs infrequently in human cancer. Science 220:1175, 1983PubMedGoogle Scholar
  51. 51.
    Finger LR, Harvey RC, Moore RCA, Showe LC, Croce CM: A common mechanism of chromosomal translocation in T-and B-cell neoplasia. Science 234:982, 1986PubMedGoogle Scholar
  52. 52.
    Forrester K, Almoguera C, Han K, Grizzle WE, Perucho M: Detection of high incidence of K-ras oncogenes during human colon tumorigenesis. Nature (London) 327:298, 1987Google Scholar
  53. 53.
    Friend SH, Bernards R, Rogelj S, Weinberg RA, Rapaport JM, Albert DM, Dryja TP: A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature (London) 323:643, 1986Google Scholar
  54. 54.
    Friend SH, Horowitz JM, Gerber MR, Wang X-F, Bogenmann E, Li FP, Weinberg RA: Deletions of a DNA sequence in retinoblastomas and mesenchymal tumors: Organization of the sequence and its encoded protein. Proc Natl Acad Sci USA 84:9059, 1987PubMedGoogle Scholar
  55. 55.
    Fung Y-K T, Murphree AL, T’Ang A, Qian J, Hinrichs SH, Benedict WF: Structural evidence for the authenticity of the human retinoblastoma gene. Science 236:1657, 1987PubMedGoogle Scholar
  56. 56.
    Gansler T, Allen KD, Burant CF, Inabnett T, Scott A, Buse MG, Sens DA, Garvin AJ: Detection of type 1 insulinlike growth factor (IGF) receptors in Wilms’ tumors. Am J Pathol 130:431, 1988PubMedGoogle Scholar
  57. 57.
    Gateff E: Malignant neoplasms of genetic origin in Drosophila melanogaster. Science 200:1448, 1978PubMedGoogle Scholar
  58. 58.
    Glaser T, Lewis WH, Bruns GAP, Watkins PC, Rogler CE, Shows TB, Powers VE, Willard HF, Goguen JM, Simola KOJ, Housman DE: The B-subunit of follicle-stimulating hormone is deleted in patients with aniridia and Wilms’ tumour, allowing a further definition of the WAGR locus. Nature (London) 321:882, 1986Google Scholar
  59. 59.
    Godbout R, Dryja TP, Squire J, Gallie BL, Phillips RA: Somatic inactivation of genes on chromosome 13 is a common event in retinoblastoma. Nature (London) 304:451, 1983Google Scholar
  60. 60.
    Goelz SE, Hamilton SR, Vogelstein B: Purification of DNA from formaldehyde fixed and paraffin embedded human tissue. Biochem Biophys Res Commun 130:118, 1985PubMedGoogle Scholar
  61. 61.
    Grady-Leopardi EF, Schwab M, Ablin AR, Rosenau W: Detection of N-myc oncogene expression in human neuroblastoma by in situ hybridization and blot analysis: relationship to clinical outcome. Cancer Res 46:3196, 1986PubMedGoogle Scholar
  62. 62.
    Green AR, Wyke JA: Anti-oncogenes: a subset of regulatory genes involved in carcinogenesis. Lancet 2:475, 1985PubMedGoogle Scholar
  63. 63.
    Grundy P, Koufos A, Morgan K, Li FP, Meadows AT, Cavenee WK: Familial predisposition to Wilms’ tumor does not map to the short arm of chromosome 11. Nature (London) 336:374, 1988Google Scholar
  64. 64.
    Gu J, Linnoila RI, Seibel NL, Gazdar AF, Minna JD, Brooks BJ, Hollis GF, Kirsch IR: A study of myc-related gene expression in small cell lung cancer by in situ hybridization. Am J Pathol 132:13, 1988PubMedGoogle Scholar
  65. 65.
    Hamlyn P, Sikora K: Oncogenes. Lancet 2:326, 1983PubMedGoogle Scholar
  66. 66.
    Hansen MF, Koufos A, Gallie BL, Phillips RA, Fodstad O, Brogger A, Gedde-Dahl T, Cavenee WK: Osteosarcoma and retinoblastoma: a shared chromosomal mechanism revealing recessive predisposition. Proc Natl Acad Sci USA 82:6212, 1985Google Scholar
  67. 67.
    Hansen MF, Cavenee WK: Genetics of cancer predisposition. Cancer Res 47:5518, 1987PubMedGoogle Scholar
  68. 68.
    Harbour JW, Lai S-L, Whang-Peng J, Gazdar AF, Minna JD, Kaye FJ: Abnormalities in structure and expression of the human retinoblastoma gene in SCLC. Science 241:353, 1988PubMedGoogle Scholar
  69. 69.
    Harper ME, Ullrich A, Saunders GF: Localization of the human insulin gene to the distal end of the short arm of chromosome 11. Proc Natl Acad Sci USA 78:4458, 1981PubMedGoogle Scholar
  70. 70.
    Harris H, Miller OJ, Klein G, Worst P, Tachiabana T: Suppression of malignancy by cell fusion. Nature (London) 223:363, 1969Google Scholar
  71. 71.
    Harris H: The genetic analysis of malignancy. J Cell Sci 4 (Suppl):431, 1986Google Scholar
  72. 72.
    Herrera L, Kakati S, Givas L, Pietrzak E, Sandberg AA: Gardner syndrome in a man with an interstitial deletion of 5q. Am J Med Genet 25:473, 1986PubMedGoogle Scholar
  73. 73.
    Hirai H, Kobayashi Y, Mano H, Hagiwara K, Maru Y, Omine M, Mizoguchi H, Nishida J, Takaku F: A point mutation at codon 13 of the N-ras oncogene in myelodysplastic syndrome. Nature (London) 327:430, 1987Google Scholar
  74. 74.
    Huebner RJ, Todaro GJ: Oncogenes of RNA tumor viruses as determinants of cancer. Proc Natl Acad Sci USA 64:1087, 1969PubMedGoogle Scholar
  75. 75.
    Huff V, Compton DA, Chao L-Y, Strong LC, dieser CF, Saunders GF: Lack of linkage of familial Wilms’ tumour to chromosomal band 11p13. Nature (London) 336:377, 1988Google Scholar
  76. 76.
    Hunter T, Sefton BM: Transforming gene product of Rous sarcoma virus phosphorylates tyrosine. Proc Natl Acad Sci USA 77:1311, 1980PubMedGoogle Scholar
  77. 77.
    Hunter T: The proteins of oncogenes. Sci Am 251:70, 1984PubMedGoogle Scholar
  78. 78.
    Hurley JB, Simon MI, Teplow DB, Robinshaw JD, Gilman AG: Homologies between signals transducing G proteins and ras gene products. Science 226:860, 1984PubMedGoogle Scholar
  79. 79.
    Jacob L, Opper M, Metzroth B, Phannavong B, Mechler BM: Structure of the 1(2)g1 gene of Drosophila and delimitation of its tumor suppressor domain. Cell 50:215, 1987PubMedGoogle Scholar
  80. 80.
    Jaffe R, Santamaria M, Yunis EJ, Tannery NH, Agostini RM, Medina J, Goodman M: The neuroectodermal tumors of bone. Am J Surg Pathol 8:885, 1984PubMedGoogle Scholar
  81. 81.
    Junien C, Turleau C, DeGrouchy J, Said R, Rethore MO, Tenconi RK, Darfier JL: Regional assignment of catalase (CAT) gene to band 11p13:association with the aniridia-Wilms’ tumor-gonado-blastoma (WAGR) complex. Annales de Genetique 23:165, 1980PubMedGoogle Scholar
  82. 82.
    Kaczmarek L: Protooncogene expression during the cell cycle. Lab Invest 54:365, 1986PubMedGoogle Scholar
  83. 83.
    Kaneko Y, Egues MC, Rowley JD: Interstitial deletion of short arm of chromosome 11 limited to Wilms’ tumor cells in a patient without aniridia. Cancer Res 41:4577, 1981PubMedGoogle Scholar
  84. 84.
    Kaneko Y, Kondo R, Rowley JD, Moohr JW, Maurer HS: Further chromosome studies on Wilms’ tumor cells of patients without aniridia. Cancer Genet Cytogenet 10:191, 1983PubMedGoogle Scholar
  85. 85.
    Kataoka T, Powers S, Cameron S, Fasano O, Goldfarb M, Broach J, Wigler M: Functional homology of mammalian and yeast RAS genes. Cell 40:19, 1985PubMedGoogle Scholar
  86. 86.
    Klein G, Klein E: Oncogene activation and tumor progression, Carcinogenesis 5:429, 1984PubMedGoogle Scholar
  87. 87.
    Klein G, Klein E: Conditioned tumorigenicity of activated oncogenes. Cancer Res 46:3211, 1986PubMedGoogle Scholar
  88. 88.
    Knudson AG: Mutation and cancerstatistical study of retinoblastoma. Proc Natl Acad Sci USA 68:820, 1971PubMedGoogle Scholar
  89. 89.
    Knudson AG: Hereditary cancer, oncogenes, and antioncogenes. Cancer Res 45:1437, 1985PubMedGoogle Scholar
  90. 90.
    Knudson AG: Genetics of human cancer. Ann Rev Genet 20:231, 1986PubMedGoogle Scholar
  91. 91.
    Kohl NE, Kanada N, Schreck RR, Bruns G, Latt SA, Gilbert F, Alt FW: Transposition and amplification of oncogene-related sequences in human neuroblastomas. Cell 35:359, 1983PubMedGoogle Scholar
  92. 92.
    Kohl NE, Gee CE, Alt FW: Activated expression of N-myc gene in human neuroblastomas and related tumors. Science 226:1335, 1984PubMedGoogle Scholar
  93. 93.
    Kohl NE, Legouy E, DePinho RA, Nisen PD, Smith RK, Gee CE, Alt FW: Human N-myc is closely related in organization and nucleotide sequence to c-myc. Nature (London) 319:73, 1986Google Scholar
  94. 94.
    Kok K, Osinga J, Carritt B, Davis MB, van der Hout AH, van der Veen AY, Landsvater RM, de Leij LFMH, Berendsen HH, Postmus PE, Poppema S, Buys CHCM: Deletion of a DNA sequence at the chromosomal region 3p21 in all major types of lung cancer. Nature (London) 330:578, 1987Google Scholar
  95. 95.
    Koufos A, Hansen MF, Lampkin BC, Workman ML, Copeland NG, Jenkins NA, Cavenee WK: Loss of alleles at loci on human chromosome 11 during genesis of Wilms’ tumour. Nature (London) 309:170, 1984Google Scholar
  96. 96.
    Koufos A, Hansen MF, Copland NG, Jenkins NA, Lampkin BC, Cavenee WK. Loss of heterozygosity in three embryonal tumours suggests a common pathogenetic mechanism. Nature (London) 316:330, 1985PubMedGoogle Scholar
  97. 97.
    Kromowitz FB, Viola MV, Chao S, Oravez S, Mishriki Y, Finkel G, Grimson R, Lundy J: Ras p21 expression in the progression of breast cancer. Hum Pathol 18:1268, 1987Google Scholar
  98. 98.
    Kurzrock R, Shtalrid M, Romero P, Kloetzer WS, Talpas M, Trujillo M, Blick M, Beran M, Gutterman JU: A novel c-abl protein product in Philadelphia-positive acute lymphoblastic leukaemia. Nature (London) 325:631, 1987Google Scholar
  99. 99.
    Land H, Parada LF, Weinberg RA: Cellular oncogenes and multistep carcinogenesis. Science 222:771, 1983PubMedGoogle Scholar
  100. 100.
    LeBeau MM: Chromosomal fragile sites and cancer-specific rearrangements. Blood 67:849, 1986Google Scholar
  101. 101.
    Leder A, Pattengale PK, Kuo A, Stewart TA, Leder P: Consequences of widespread deregulation of the c-myc gene in transgenic mice: Multiple neoplasms and normal development. Cell 45:485, 1988Google Scholar
  102. 102.
    Leder P, Battey J, Lenoir G, Moulding C, Murphy R, Potter H, Stewart T, Taub R: Translocations among antibody genes in human cancer. Science 222:765, 1983PubMedGoogle Scholar
  103. 103.
    Lee EYHP, To H, Shew J-Y, Bookstein R, Scully P, Lee W-H: Inactivation of the retinoblastoma susceptibility gene in human breast cancers. Science 241:218, 1988PubMedGoogle Scholar
  104. 104.
    Lee W-H, Bookstein R, Hong F, Young L-J, Shew J-Y, Lee EYHP: Human retinoblastoma susceptibility gene: cloning, identification and sequence. Science 235:1394, 1987PubMedGoogle Scholar
  105. 105.
    Lee W-H, Shew J-Y, Hong FD, Sery TW, Donoso LA, Young L-J, Bookstein R, Lee EYHP: The retinoblastoma susceptibility gene encodes a nuclear phosphoprotein associated with DNA binding activity. Nature (London) 329:642, 1987Google Scholar
  106. 106.
    Leibowitz RM: Oncogenes as mediators of cell growth and differentiation. Lab Invest 55:249, 1986Google Scholar
  107. 107.
    Lele KP, Penrose LS, Stallard HB: Chromosome deletion in a case of retinoblastoma. Am J Human Genet 27:171, 1963Google Scholar
  108. 108.
    Leppert M, Dobbs M, Scambler P, O’Connell P, Nakamura Y, Stauffer D, Woodward S, Burt R, Hughes J, Gardner E, Lathrop M, Wasmuth J, Lalouel J-M, White R: The gene for familial polyposis coli maps to the long arm of chromosome 5. Science 238:1411, 1987PubMedGoogle Scholar
  109. 109.
    Little CD, Nau MM, Carney DN, Gazdar AF, Minna JD: Amplification and expression of the c-myc oncogene in human lung cancer cell lines. Nature (London) 306:194, 1983Google Scholar
  110. 110.
    Lundberg C, Skoog L, Cavenee WK, Nordenskjold M: Loss of heterozygosity in human ductal breast tumors indicates a recessive mutation on chromosome 13. Proc Natl Acad Sci USA 84:2372, 1987PubMedGoogle Scholar
  111. 111.
    Manolov G, Manolova Y: Marker band in one chromosome 14 from Burkitt lymphomas. Nature (London) 237:33, 1972Google Scholar
  112. 112.
    Martin GS: Rous sarcoma virus: a function required for the maintenance of the transformed state. Nature (London) 227:1021, 1970Google Scholar
  113. 113.
    Mathew CGP, Smith BA, Thorpe K, Wong Z, Royle NJ, Jeffreys AJ, Ponder BAJ: Depletion of genes on chromosome 1 in endocrine neoplasia. Nature (London) 328:524, 1987Google Scholar
  114. 114.
    Mathew CGP, Chin KS, Easton DF, Thorpe K, Cater C, Liou GI, Fong S-L, Bridges CDB, Haak H, Nieuwenhuijzen Kruseman AC, Schifter S, Hansen HH, Telenius H, Telenius-Berg M, Ponder BAJ: A linked genetic marker for multiple endocrine neoplasia type 2A on chromosome 10. Nature (London) 328:527, 1987Google Scholar
  115. 115.
    McKeithan TW, Shima EA, LeBeau MM, Minowada J, Rowley JD, Diaz MO: Molecular cloning of the breakpoint junction of a human chromosomal 8;14 translocation involving the T-cell receptor alpha-chain gene and sequences on the 3′ side of MYC. Proc Natl Acad Sci USA 83:6636, 1986PubMedGoogle Scholar
  116. 116.
    Mendoza AE, Shew J-Y, Lee EVHP, Bookstein R, Lee W-H: A case of synovial sarcoma with abnormal expression of the human retinoblastoma gene. Human Pathol 19:487, 1988Google Scholar
  117. 117.
    Miller RW, Fraumeni JF, Manning MD: Association of Wilms’ tumor with aniridia, hemihypertrophy and other congenital malformations. N Engl J Med 270:922, 1964PubMedGoogle Scholar
  118. 118.
    Mitelman F: Restricted number of chromosomal regions implicated in aetiology of human cancer and leukemia. Nature (London) 310:325, 1984Google Scholar
  119. 119.
    Muleris M, Salmon RJ, Zafrani B, Girodet J, Dutrillaux B: Consistent deficiencies of chromosome 18 and of the short arm of chromosome 17 in eleven cases of human large bowel cancer: a possible recessive determinism. Ann Genet (Paris) 28:206, 1985Google Scholar
  120. 120.
    Nau MM, Brooks Jr BJ, Carney DN, Gazdar AF, Battey JF, Sausville EA, Minna JD: Human small-cell lung cancers show amplification and expression of the N-myc gene. Proc Natl Acad Sci USA 83:1092, 1986PubMedGoogle Scholar
  121. 121.
    Naylor SL, Johnson BE, Minna JD, Sakaguchi AY: Loss of heterozygosity of chromosome 3p markers in small-cell lung cancer. Nature (London) 329:451, 1987Google Scholar
  122. 122.
    Ngan B-Y, Chen-Levy Z, Weiss LM, Warnke RA, Cleary ML: Expression in non-Hodgkin’s lymphoma of the bcl-2 protein associated with the t(14;18) chromosomal translocation. N Engl J Med 318:1638, 1988PubMedGoogle Scholar
  123. 123.
    Nisen PD, Zimmerman KA, Cotter SV, Gilbert F, Alt FW: Enhanced expression of the N-myc gene in Wilms’ tumors. Cancer Res 46:6217, 1986PubMedGoogle Scholar
  124. 124.
    Nowell PC, Hungerford DA: A minute chromosome in human chronic granulocytic leukemia. Science 132:1497, 1960Google Scholar
  125. 125.
    Nowell PC, Croce CM: Chromosomes, genes, and cancer. Am J Pathol 125:8, 1986Google Scholar
  126. 126.
    Nunberg JK, Kaufman RJ, Schimke RT, Urlaub G, Chasin LA: Amplified dihydrofolate reductase genes are localized to a homogenously staining region of a single chromosome in a methotrexateresistant Chinese hamster ovary cell line. Proc Natl Acad Sci USA 75:5553, 1978PubMedGoogle Scholar
  127. 127.
    Ohno S: Genetic implication of karyological instability of malignant somatic cells. Physiol Rev 51:496, 1971Google Scholar
  128. 128.
    Okamoto M, Sasaki M, Sugio K, Sato C, Iwama T, Ikeuchi T, Tonomura A, Sasazuki T, Miyaki M: Loss of constitutional heterozygosity in colon carcinoma from patients with familial polyposis coli. Nature (London) 331:273, 1988Google Scholar
  129. 129.
    Orkin SH, Goldman DS, Sallan SE: Development of homozygosity for chromosome 11p markers in Wilms’ tumour. Nature (London) 309:172, 1984Google Scholar
  130. 130.
    Ponder B. Gene losses in human tumours. Nature (London) 335:400, 1988Google Scholar
  131. 131.
    Potluri VR, Gilbert F, Helson L: Neuroectodermal tumors: chromosomal changes and gene amplification. Am J Hum Genet 36:345, 1984Google Scholar
  132. 132.
    Reddy EP, Reynolds RK, Santos E, Barbacid M: A point mutation is responsible for the acquisition of transforming properties by the T24 human bladder cancer oncogene. Nature (London) 300:149, 1982Google Scholar
  133. 133.
    Reed JC, Cuddy M, Slabiak T, Croce M, Nowell PC: Oncogenic potential of bcl-2 demonstrated by gene transfer. Nature (London) 336:259, 1988Google Scholar
  134. 134.
    Reeve AE, Housiaux PJ, Gardner RJM, Chewings WE, Grindley RM, Millow LJ: Loss of a Harvey ras allele in sporadic Wilms’ tumour. Nature (London) 309:174, 1984Google Scholar
  135. 135.
    Reeve AE, Eccles MR, Wilkins RJ, Bell GI, Millow LJ: Expression of insulin-like growth factor-II transcripts in Wilms’ tumour. Nature (London) 317:258, 1985Google Scholar
  136. 136.
    Reichmann A, Martin P, Levin B: Chromosomal banding patterns in human large bowel cancer. Int J Cancer 28:431, 1981PubMedGoogle Scholar
  137. 137.
    Riccardi VM, Sujansky E, Smith AC, Francke U: Chromosomal imbalance in the aniridia-Wilms tumor association:llp interstitial deletion. Pediatrics 61:604, 1979Google Scholar
  138. 138.
    Rodenhuis S, van de Wetering ML, Mooi WJ, Evers SG, van Zandwijk N, Bos JL: Mutational activation of the K-ras oncogene. N Engl J Med 317:929, 1987PubMedGoogle Scholar
  139. 139.
    Rootman J, Carruthers JDA, Miller RR: Retinoblastoma. Perspect Pediatr Pathol 10:208, 1987PubMedGoogle Scholar
  140. 140.
    Rouleau GA, Wertelecki W, Haines JL, Hobbs WJ, Trofatter JA, Seizinger BR, Martuza RL, Superneau DW, Conneally PM, Gusella JF: Genetic linkage of bilateral acoustic neurofibromatosis to a DNA marker on chromosome 22. Nature (London) 329:246, 1987Google Scholar
  141. 141.
    Rous P: A sarcoma of the fowl transmissible by an agent separable from the tumor cells. J Exp Med 13:397, 1911PubMedGoogle Scholar
  142. 142.
    Rowley JD: A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and giemsa staining. Nature (London) 243:290, 1973Google Scholar
  143. 143.
    Sager R: Genetic suppression of tumor formation: A new frontier in cancer research. Cancer Res 46:1573, 1986PubMedGoogle Scholar
  144. 144.
    Schroeder WT, Chao L-Y, Dao DD, Strong LC, Pathak S, Riccardi V, Lewis WH, Saunders GF: Nonrandom loss of maternal chromosome 11 alleles in Wilms tumours. Am J Human Genet 40:413, 1987Google Scholar
  145. 145.
    Schwab M, Alitalo K, Varmus HE, Bishop MJ, George D: A cellular oncogene (c-Ki-ras) is amplified, overexpressed, and located within karyotypic abnormalities in mouse adrenocortical tumour cells. Nature (London) 303:497, 1983Google Scholar
  146. 146.
    Schwab M, Alitalo K, Klempnauer K-H, Varmus HE, Bishop JM, Gilbert F, Brodeur G, Goldstein M, Trent J: Amplified DNA with limited homology to myc cellular oncogene is shared by human neuroblastoma cell lines and a neuroblastoma tumour. Nature (London) 305:245, 1983Google Scholar
  147. 147.
    Schwab M, Ellison J, Busch M, Rosenau W, Varmus HE, Bishop JM: Enhanced expression of the human gene N-myc consequent to amplification of DNA may contribute to malignant progression of neuroblastoma. Proc Natl Acad Sci USA 81:4940, 1984PubMedGoogle Scholar
  148. 148.
    Scrabble HJ, Witte DP, Lampkin BC, Cavenee WK: Chromosomal localization of the human rhabdomyosarcoma locus by mitotic recombination mapping. Nature (London) 329:645, 1987Google Scholar
  149. 149.
    Seeger RC, Brodeur GM, Sather H, Dalton A, Siegel SE, Wong KY, Hammond D: Association of multiple copies of the n-myc oncogene with rapid progression of neuroblastomas. N Engl J Med 313:1111, 1985PubMedGoogle Scholar
  150. 150.
    Seemayer TA, de Chadarévian J-P, Vekemans M: Histological and cytogenetic findings in a malignant tumor of the chest wall and lung (Askin tumor). Virchows Arch [A] 408:289, 1985Google Scholar
  151. 151.
    Seizinger BR, Martuza RL, Gusella JF: Loss of genes on chromosome 22 in tumorigenesis of human acoustic neuroma. Nature (London) 322:644, 1986Google Scholar
  152. 152.
    Seizinger BR, Rouleau G, Ozelius LJ, Lane AH, St George-Hyslop P, Huson S, Gusella JF, Martuza RL: Common pathogenetic mechanism for three tumour types in bilateral acoustic neurofibromatosis. Science 236:317, 1987PubMedGoogle Scholar
  153. 153.
    Seizinger BR, Rouleau GA, Ozelius LJ, Lane AH, Faryniarz AG, Chao MV, Huson S, Korf BR, Parry DM, Pericak-Vance MA, Collins FS, Hobbs WJ, Falcone BG, Iannazzi JA, Roy JC, St George-Hyslop PH, Tanzi RE, Bothwell MA, Upadhyaya M, Harper P, Goldstein AE, Hoover DL, Bader JL, Spence MA, Mulvihill JJ, Aylsworth AS, Vance JM, Rossenwasser GOD, Gaskell PC, Roses AD, Martuza RL, Breakefield XO, Gusella JF: Genetic linkage of von Recklinghausen neurofibromatosis to the nerve growth factor receptor gene. Cell 49:589, 1987PubMedGoogle Scholar
  154. 154.
    Seizinger BR, Rouleau GA, Ozelius LJ, Lane AH, Farmer GE, Lamiell JM, Haines J, Yuen JWM, Collins D, Majoor-Krakauer D, Bonner T, Mathew C, Rubenstein A, Halperin J, McConkie-Rosell A, Green JS, Trofatter JA, Ponder BA, Eierman L, Bowmer MI, Schimke R, Oostra B, Aronin N, Smith DI, Drabkin H, Waziri MH, Hobbs WJ, Martuza RL, Conneally PM, Hsia YE, Gusella JF: Von-Hippel-Lindau disease maps to the region of chromosome 3 associated with renal cell carcinoma. Nature (London) 332:268, 1988Google Scholar
  155. 155.
    Shih C, Shilo BZ, Goldfarb MP, Dannenberg A, Weinberg RA: Passage of phenotypes of chemically transformed cells via transfection of DNA and chromatin. Proc Natl Acad Sci USA 76:5714, 1979PubMedGoogle Scholar
  156. 156.
    Slamon DJ, de Kernion JB, Verma IM, Cline MJ: Expression of cellular oncogenes in human malignancies. Science 224:256, 1984PubMedGoogle Scholar
  157. 157.
    Slamon DJ, Boone TC, Seeger RC, Keith DE, Chazin V, Lee HC, Souza LM: Identification and characterization of the protein encoded by the human N-myc oncogene. Science 232:768, 1986PubMedGoogle Scholar
  158. 158.
    Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL: Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235:177, 1987PubMedGoogle Scholar
  159. 159.
    Slamon DJ, Clark GM: Response. Science 240:1796, 1988PubMedGoogle Scholar
  160. 160.
    Solomon E, Voss R, Hall V, Bodmer WF, Jass JR, Jeffreys AJ, Lucibello FC, Patel I, Rider SH: Chromosome 5 allele loss in human colorectal carcinomas. Nature (London) 328:616, 1987Google Scholar
  161. 161.
    Sotelo-Avila C, Gooch WM: Neoplasms associated with the Beck-with-Wiedemann syndrome. In Perspectives in Pediatric Pathology, Vol 3, edited by Rosenberg HS, Bolande RP, pp 255–272. Chicago, Year Book Medical Publishers, 1976Google Scholar
  162. 162.
    Sparkes RS, Sparkes MD, Wilson MA, Towner JW, Benedict W, Murphree AL, Yunis JJ: Regional assignment of genes for human esterase-D and retinoblastoma to chromosome band 13q14. Science 208:1042, 1980PubMedGoogle Scholar
  163. 163.
    Sparkes RS, Murphree AL, Lingua RW, Sparkes MD, Field LL, Funderburk SJ, Benedict WF: Gene for hereditary retinoblastoma assigned to human chromosome 13 by linkage to esterase-D. Science 219:971, 1983PubMedGoogle Scholar
  164. 164.
    Spector D, Varmus HE, Bishop JM: Nucleotide sequences related to the transforming gene of ASV are present in DNA of uninfected vertebrates. Proc Natl Acad Sci USA 75:4102, 1978PubMedGoogle Scholar
  165. 165.
    Stanbridge EJ: Suppression of malignancy in human cells. Nature (London) 260:17, 1976Google Scholar
  166. 166.
    Stanton LW, Schwab M, Bishop JM: Nucleotide sequence of the human N-myc gene. Proc Natl Acad Sci USA 83:1772, 1986PubMedGoogle Scholar
  167. 167.
    Suhumar S, Notario V, Martin-Zanca D, Barbacid M: Induction of mammary carcinomas in rats by nitroso-methylurea involves malignant activation of H-ras-1 locus by single point mutations. Nature (London) 306:658, 1983Google Scholar
  168. 168.
    T’Ang A, Varley JM, Chakraborty S, Murphree AL, Fung Y-KT: Structural rearrangement of the retinoblastoma gene in human breast carcinoma. Science 242:263, 1988PubMedGoogle Scholar
  169. 169.
    Temin HM, Mizutani S: RNA-dependent DNA polymerase in virions of Rous sarcoma virus. Nature (London) 226:1211, 1970Google Scholar
  170. 170.
    Tsuda H, Shimosato Y, Upton MP, Yokota J, Terada M, Ohira M, Sugimura T, Hirohashi S: Retrospective study on amplification of N-myc and c-myc genes in pediatric solid tumors and its association with prognosis and tumor differentiation. Lab Invest 59:321, 1988PubMedGoogle Scholar
  171. 171.
    Tsujimoto Y, Cossman J, Jaffe E, Croce CM: Involvement of the bcl-2 gene in human follicular lymphoma. Science 228:1440, 1985PubMedGoogle Scholar
  172. 172.
    Turc-Carel C, Philip I, Berger M-P, Philip T, Lenoir GM: Chromosomal translocations in Ewing’s sarcoma. N Engl J Med 309:497, 1983Google Scholar
  173. 173.
    Turleau C, De Grouchy J, Chavin-Colin F, Martelli H, Voyer J, Charlas R: Trisomy 11p15 and Beckwith-Wiedemann syndrome: a report of two cases. Human Genet 67:219, 1984Google Scholar
  174. 174.
    Varmus HE: The molecular genetics of cellular oncogenes. Ann Rev Genet 18:553, 1984PubMedGoogle Scholar
  175. 175.
    Venter DJ, Kumar S, Tuzi NL, Gullick WJ: Overexpression of the c-erbB-2 oncoprotein in human breast carcinomas: immunohistological assessment correlates with gene amplification. Lancet 2:69, 1987PubMedGoogle Scholar
  176. 176.
    Verma IM: Proto-oncogene fos: a multifaceted gene. Trends in Genetics 2:93, 1986Google Scholar
  177. 177.
    Vogelstein B, Fearon ER, Hamilton SR, Kern SE, Preisinger AC, Leppert M, Nakamura Y, White R, Smits AMM, Bos JL: Genetic alterations during colorectal-tumor development. N Engl J Med 319:525, 1988PubMedGoogle Scholar
  178. 178.
    Vogt M, Dulbecco R: Steps in the neoplastic transformation of hamster embryo cells by polyoma virus. Proc Natl Acad Sci USA 49:171, 1963PubMedGoogle Scholar
  179. 179.
    Waziri M, Patil SR, Hanson JW, Bartley JA: Abnormality of chromosome 11 in patients with features of Beckwith-Wiedemann syndrome. J Pediatr 102:873, 1983PubMedGoogle Scholar
  180. 180.
    Weinberg RA: A molecular basis for cancer. Sci Am 249:126, 1983PubMedGoogle Scholar
  181. 181.
    Weinberg RA: Oncogenes and the mechanisms of carcinogenesis. Sci Am Med Section 12, II pp 1–10, 1984Google Scholar
  182. 182.
    Weiss LM, Warnke RA, Sklar J, Cleary ML: Molecular analysis of the t(14;18) chromosomal translocation in malignant lymphomas. N Engl J Med 317:1185, 1987PubMedGoogle Scholar
  183. 183.
    Weiss RA, Marshall CJ: Oncogenes. Lancet 2:1138, 1984PubMedGoogle Scholar
  184. 184.
    Weissman BE, Saxon PJ, Pasquale SR, Jones GR, Geiser AG, Stanbridge EJ: Introduction of a normal human chromosome 11 into a Wilms’ tumor cell line controls its tumorigenic expression. Science 236:175, 1987PubMedGoogle Scholar
  185. 185.
    Whang-Peng J, Triche TJ, Knutsen T, Miser J, Douglass EC, Israel MA: Chromosomal translocation in peripheral neuroepithelioma. N Engl J Med 311:584, 1984PubMedGoogle Scholar
  186. 186.
    Whyte P, Buchkovich KJ, Horowitz JM, Friend SH, Raybuck M, Weinberg RA, Harlow E: Association between an oncogene and an anti-oncogene: The adenovirus E1A proteins bind to the retinoblastoma gene product. Nature (London) 334:124, 1988Google Scholar
  187. 187.
    Wiedemann HR: Complexe malformatif familial avec hernie ombilicale et macroglossie: un “syndrome nouveau?” J Genet Hum 13:223, 1964PubMedGoogle Scholar
  188. 188.
    Wiggs J, Nordensjöld M, Yandell D, Rapaport J, Grondin V, Janson M, Werelius B, Petersen R, Craft A, Riedel K, Liberfarb R, Walton D, Wilson W, Dryja TP: Prediction of the risk of hereditary retinoblastoma, using DNA polymorphisms within the retinoblastoma gene. N Engl J Med 318:151, 1988PubMedGoogle Scholar
  189. 189.
    Wilkins RJ: Genomic imprinting and carcinogenesis. Lancet 1:329, 1988PubMedGoogle Scholar
  190. 190.
    Williman CL, Fenoglio-Preiser CM: Oncogenes, suppressor genes, and carcinogenesis. Hum Pathol 18:895, 1987Google Scholar
  191. 191.
    Wong AJ, Ruppert JM, Eggleston J, Hamilton SR, Baylin SB, Vogelstein B: Gene amplification of c-myc and N-myc in small cell carcinoma of the lung. Science 233:461, 1986PubMedGoogle Scholar
  192. 192.
    Yokota J, Tsunetsugu-Yokota Y, Battifora H, LeFevre C, Cline MJ: Alterations of myc, myb, and ras-Ha proto-oncogenes in cancers are frequent and show clinical correlation. Science 231:261, 1986PubMedGoogle Scholar
  193. 193.
    Yokota J, Wada M, Shimosato Y, Terada M, Sugimura T: Loss of heterozygosity on chromosomes 3, 13 and 17 in small-cell carcinoma and on chromosome 3 in adenocarcinoma of the lung. Proc Natl Acad Sci USA 84:9252, 1987PubMedGoogle Scholar
  194. 194.
    Yunis JJ, Ramsay N: Retinoblastoma and subband deletion on chromosome 13. Am J Dis Child 132:161, 1978PubMedGoogle Scholar
  195. 195.
    Yunis JJ, Bloomfield CD, Ensrud K: All patients with acute nonlymphocytic leukemia may have a chromosomal defect. N Engl J Med 305:135, 1981PubMedGoogle Scholar
  196. 196.
    Yunis JJ: The chromosomal basis of human neoplasia. Science 221:227, 1983PubMedGoogle Scholar
  197. 197.
    Yunis JJ: Fragile sites and predisposition to leukemia and lymphoma. Cancer Genet Cytogenet 12:85, 1984PubMedGoogle Scholar
  198. 198.
    Zbar B, Brauch H, Talmadge C, Linehan M: Loss of alleles of loci on the short arm of chromosome 3 in renal cell carcinoma. Nature 327:721, 1987PubMedGoogle Scholar
  199. 199.
    Zhou D, Battifora H, Yokota J, Yamamoto T, Cline MJ: Association of multiple copies of the c-erbB-2 oncogene with spread of breast cancer. Cancer Res 47:6123, 1987PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1990

Authors and Affiliations

  • Thomas A. Seemayer
    • 1
  • Webster K. Cavenee
    • 1
  1. 1.Departments of Pathology, Pediatrics and MedicineMcGill University Faculty of Medicine, The Montreal Children’s Hospital and Ludwig Institute for Cancer Research (Montreal Branch)UK

Personalised recommendations