Reviews of chromosome studies in urological tumors. III. Cytogenetics and genes in testicular tumors

Journal of Urology

Volumn 155, Issue 5, 1996, Pages 1531-1556

  Sandberg, Avery A ^a   Meloni, Aurelia M ^a   Suijkerbuijk, Ron F ^a,b  

^a GENZYME CORPORATION   (United States)

^b RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

cytogenetics; germ cells; testicular neoplasms

Indexed keywords

CANCER GRADING; CARCINOMA IN SITU; CHORIOCARCINOMA; CHROMOSOME 12; CHROMOSOME ANALYSIS; CYTOGENETICS; FLOW CYTOMETRY; FLUORESCENCE IN SITU HYBRIDIZATION; GENETIC HETEROGENEITY; HUMAN; NEUROEPITHELIOMA; PLEOMORPHIC ADENOMA; PRIORITY JOURNAL; RECURRENT CANCER; REVIEW; SEMINOMA; TERATOMA; TESTIS TUMOR; TUMOR SUPPRESSOR GENE;

EID: 0029931790     PISSN: 00225347     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0022-5347(01)66124-X     Document Type: Review

References (254)

1. Mostofi, F. K. and Price, E. B.: Tumors of the male genital system. In: Atlas of Tumor Pathology. Washington, D. C.: Armed Forces Institute of Pathology, 2nd series, fasc. 8, 1973.
2. Scully, R. E.: Tumors of the ovary and maldeveloped gonads. In: Atlas of Tumor Pathology. Washington, D. C.: Armed Forces Institute of Pathology, 2nd series, fasc. 16, 1979.
3. Gonzales-Crussi, F.: Extragonadal teratomas. In: Atlas of Tumor Pathology. Washington, D. C.: Armed Forces Institute of Pathology, 2nd series, fasc. 18, 1982.
4. Jacobsen, G. K. and Nørgaard-Pedersen, B.: Placental alkaline phosphatase in testicular germ cell tumours and in carcinoma-in-situ of the testis. An immunohistochemical study. Acta Path. Microbiol. Immunol. Scand., 92: 323, 1984.
5. Skakkebaek, N. E., Berthelsen, J. G., Giwercman, A. and Müller, J.: Carcinoma-in-situ of the testis: possible origin from gonocytes and precursor of all types of germ cell tumours except spermatocytoma. Int. J. Androl., 10: 19, 1987.
6. Collins, D. H. and Pugh, R. C. B.: The pathology of testicular tumours. Brit. J. Urol., suppl., 36: 1, 1964.
7. Ulbright, T. M. and Roth, L. M.: Recent developments in the pathology of germ cell tumors. Sem. Diag. Path., 4: 304, 1987.
8. Mostofi, F. K., Sesterhenn, I. A. and Davis, C. J., Jr.: Immunopathology of germ cell tumors of the testis. Sem. Diag. Path., 4: 320, 1987.
9. Harms, D. and Jänig, U.: Germ cell tumors of childhood. Report of 170 cases including 59 pure and partial yolk-sac tumors. Virchows Arch. A, 409: 223, 1986.
10. Oosterhuis, J. W., Castedo, S. M. and de Jong, B.: Cytogenetics, ploidy and differentiation of human testicular, ovarian and extragonadal germ cell tumours. Cancer Surv., 9: 321, 1990.
11. Koide, O., Iwai, S., Baba, K. and Iri, H.: Identification of testicular atypical germ cells by an immunohistochemical technique for placental alkaline phosphatase. Cancer, 60: 1325, 1987.
12. Müller, J., Skakkebaek, N. E. and Parkinson, M. C.: The spermatocytic seminoma: views on pathogenesis. Int. J. Androl., 10: 147, 1987.
13. Javadpour, N.: The National Cancer Institute experience with testicular cancer. J. Urol., 120: 651, 1978.
14. Schottenfeld, D., Warshauer, M. E., Sherlock, S., Zouter, A. G., Leder, M. and Payne, R.: The epidemiology of testicular cancer in young adults. Amer. J. Epidemiol., 112: 232, 1980.
15. Oliver, R. T.: Clues from natural history and results of treatment supporting the monoclonal origin of germ cell tumours. Cancer Surv., 9: 333, 1990.
16. Pugh, R. C. B.: Combined tumours. In: Pathology of the Testis. Oxford: Blackwell Scientific, pp. 245-258, 1976.
17. Oosterhuis, J. W., Castedo, S. M., de Jong, B., Cornelisse, C. J., Dam, A., Sleijfer, D. T. and Schraffordt Koops, H.: Ploidy of primary germ cell tumors of the testis. Pathogenetic and clinical relevance. Lab. Invest., 60: 14, 1989.
18. Krabbe, S., Skakkebaek, N. E., Berthelsen, J. G., Eyben, F. V., Volsted, P., Mauritzen, K., Eldrup, J. and Nielsen, A. H.: High incidence of undetected neoplasia in maldescended testes. Lancet, 1: 999, 1979.
19. Einhorn, L. H., Donohue, J. P., Peckham, M. J., Williams, S. D. and Loehrer, P. J.: Cancer of the testes. In: Cancer: Principles and Practice of Oncology. Edited by V. T. DeVita, S. Hellman and S. A. Rosenberg. Philadelphia: J. B. Lippincott Co., vol. 2, chapt. 31, pp. 979-1011, 1985.
20. Lachman, M. F., Kim, K. and Koo, B. C.: Mediastinal teratoma associated with Klinefelter's syndrome. Arch. Path. Lab. Med., 110: 1067, 1986.
21. Andrews, P. W.: Retinoic acid induces neuronal differentiation of a cloned human embryonal carcinoma cell line in vitro. Dev. Biol., 103: 285, 1984.
22. Mostofi, F.: Proceedings: testicular tumors. Epidemiologie, etiologic and pathologic features. Cancer, 32: 1186, 1973.
23. Talerman, A.: Endodermal sinus (yolk sac) tumor elements in testicular germ-cell tumors in adults: comparison of prospective and retrospective studies. Cancer, 48: 1213, 1980.
24. Rosai, J., Khodadoust, K. and Silber, I.: Spermatocytic seminoma: II. Ultrastructural study. Cancer, 24: 103, 1969.
25. Dekker, I., Rozeboom, T., Dam, A., Delemarre, J. and Oosterhuis, J. W.: Placental-like alkaline phosphatase and DNA flow cytometry in spermatocytic seminoma. Cancer, 69: 993, 1992.
26. Mostofi, F. K.: Pathology of germ cell tumors of testis: a progress report. Cancer, suppl., 45: 1735, 1980.
27. Atkin, N. B. and Baker, M. C.: i(12p): A specific chromosomal marker in seminoma and malignant teratoma of the testis? Cancer Genet. Cytogenet., 10: 199, 1983.
28. Gibas, Z., Prout, G. R., Pontes, J. E. and Sandberg, A. A.: Chromosome changes in germ cell tumors of the testis. Cancer Genet. Cytogenet., 19: 245, 1986.
29. Castedo, S. M., de Jong, B., Oosterhuis, J. W., Idenburg, V. J., Seruca, R., Buist, J., te Meerman, G. J., Schraffordt Koops, H. and Sleijfer, D. T.: Chromosomal changes in mature residual teratomas following polychemotherapy. Cancer Res., 49: 672, 1989.
30. Castedo, S. M., de Jong, B., Oosterhuis, J. W., Seruca, R., te Meerman, G. J., Dam, A. and Schraffordt Koops, H.: Cytogenetic analysis of ten human seminomas. Cancer Res., 49: 439, 1989.
31. Castedo, S. M., de Jong, B., Oosterhuis, J. W., Seruca, R., Idenburg, V. J., Dam, A., te Meerman, G. J., Schraffordt Koops, H. and Sleijfer, D. T.: Chromosomal changes in primary testicular nonseminomatous germ cell tumors. Cancer Res., 49: 5696, 1989.
32. Rodriguez, E., Mathew, S., Reuter, V. E., Ilson, D. H., Bosl, G. J. and Chaganti, R. S.: Cytogenetic analysis of 124 prospectively ascertained male germ cell tumors. Cancer Res., 52: 2285, 1992.
33. Samaniego, F., Rodriguez, F., Houldsworth, J., Murty, V. V., Ladanyi, M., Lele, K. P., Chen, Q. G., Dmitrovsky, E., Geller, N. L., Reuter, V., Jhanwar, S. C., Bosl, G. J. and Chaganti, R. S.: Cytogenetic and molecular analysis of human male germ cell tumors: chromosome 12 abnormalities and gene amplification. Genes Chrom. Cancer, 1: 289, 1990.
34. Gibas, Z., Prout, G. R., Jr. and Sandberg, A. A.: Malignant teratoma of the testis with an isochromosome no. 12, i(12p), as the sole structural cytogenetic abnormality. J. Urol., 131: 762, 1984.
35. Atkin, N. B., Fox, M. F., Baker, M. C. and Jackson, Z.: Chromosome 12-containing markers, including two dicentrics, in three i(12p)-negative testicular germ cell tumors. Genes Chrom. Cancer, 6: 218, 1993.
36. Rodriguez, E., Houldsworth, J., Reuter, V. E., Meltzer, P., Zhang, J., Trent, J. M., Bosl, G. J. and Chaganti, R. S.: Molecular cytogenetic analysis of i(12p)-negative human male germ cell tumors. Genes Chrom. Cancer, 8: 230, 1993.
37. Haddad, F. S., Sorini, P. M., Somsin, A. A., Nathan, M. H., Dobbs, R. M., Berger, C. S. and Sandberg, A. A.: Familial double testicular tumors: identical chromosome changes in seminoma and embryonal carcinoma of the same testis. J. Urol., 139: 748, 1988.
38. Castedo, S. M., de Jong, B., Oosterhuis, J. W., Seruca, R., Buist, J. and Schraffordt Koops, H.: Cytogenetic study of a combined germ cell tumor of the testis. Cancer Genet. Cytogenet., 35: 159, 1988.
39. Vos, A., Oosterhuis, J. W., de Jong, B., Buist, J. and Schraffordt Koops, H.: Cytogenetics of carcinoma in situ of the testis. Evidence for a nonrandom distribution of normal chromosomes. Cancer Genet. Cytogenet., 46: 75, 1990.
40. Atkin, N. B. and Baker, M. C.: Numerical chromosome changes in 165 malignant tumors. Cancer Genet. Cytogenet., 52: 113, 1991.
41. Neerman-Arbez, M., Delozier-Blanchet, C. D., Bolle, J. F., Rendez, R. and Morris, M.: High incidence of ectopic nucleolar organizer regions in human testicular tumors. Cancer Genet. Cytogenet., 65: 58, 1993.
42. Sonta, S., Oshimura, M., Evans, J. T. and Sandberg, A. A.: Chromosomes and causation of human cancer and leukemia. XX. Banding patterns of primary tumors. J. Natl. Cancer Inst., 58: 49, 1977.
43. Atkin, N. B. and Baker, M. C.: Chromosome analysis of three seminomas. Cancer Genet. Cytogenet., 17: 315, 1985.
44. Delozier-Blanchet, C. D., Engel, E. and Walt, H.: Isochromosome 12p in malignant testicular tumors. Letter to the Editor. Cancer Genet. Cytogenet., 15: 375, 1985.
45. Oosterhuis, J. W., Castedo, S. M., de Jong, B., Seruca, R., Dam, A., Vos, A. M., de Koning, J., Schraffordt Koops, H. and Sleijfer, D. T.: A malignant mixed gonadal stromal tumor of the testis with heterologous components and i(12p) in one of its metastases. Cancer Genet. Cytogenet., 41: 105, 1989.
46. de Graaff, W. E., Oosterhuis, J. W., de Jong, B., van EchtenArends, J., Wiersema-Buist, J., Schraffordt Koops, H. and Sleijfer, D. T.: Cytogenetic analysis of the mature teratoma and the choriocarcinoma component of a testicular mixed nonseminomatous germ cell tumors. Cancer Genet. Cytogenet., 61: 67, 1991.
47. Suijkerbuijk, R. F., Sinke, R. J., Meloni, A. M., Parrington, J. M., van Echten, J., de Jong, B., Oosterhuis, J. W., Sandberg, A. A. and Geurts van Kessel, A.: Overrepresentation of chromosome 12p sequences and karyotypic evolution in i(12p)-negative testicular germ cell tumors revealed by fluorescence in situ hybridization. Cancer Genet. Cytogenet., 70: 85, 1993.
48. Reilly, P. A., Heerema, N. A., Sledge, G. W., Jr. and Palmer, C. G.: Unusual distribution of chromosome 12 in a testicular germ-cell tumor cell line (833K) and its cisplatin-resistant derivative (64CP9). Cancer Genet. Cytogenet., 68: 114, 1993.
49. Saikevych, I. A., Mayer, M., Brooks, V. P. and Michael, S.: Cytogenetic study of a testicular tumor in a translocation (13;14) carrier. Cancer Genet. Cytogenet., 26: 299, 1987.
50. van Echten, J., Oosterhuis, J. W., Looijenga, L. H. J., van de Pol, M., Wiersema, J., te Meerman, G. J., Schraffordt Koops, H., Sleijfer, D. Th. and de Jong, B.: No recurrent structural abnormalities apart from i(12p) in primary germ cell tumors of the adult testis. Genes, Chrom. Cancer, 14: 133, 1995.
51. Chaganti, R. S., Ladanyi, M., Samaniego, F., Reuter, V. E., Jhanwar, S. C. and Bosl, G. J.: Leukemic differentiation of a mediastinal germ cell tumor. Genes, Chrom. Cancer, 1: 83, 1989.
52. Atkin, N. B. and Baker, M. C.: Specific chromosome change, i(12p), in testicular tumours? Lancet, 2: 1349, 1982.
53. Sandberg, A. A.: The Chromosomes in Human Cancer and Leukemia, 2nd ed. New York: Elsevier North Holland, 1990.
54. Dmitrovsky, E., Bosl, G. J. and Chaganti, R. S.: Clinical and genetic features of human germ cell cancer. Cancer Surv., 9: 369, 1990.
55. Bosl, G. J., Dmitrovsky, E., Reuter, V. E., Samaniego, F., Rodriguez, E., Geller, N. L. and Chaganti, R. S.: Isochromosome of chromosome 12: clinically useful marker for male germ cell tumors. J. Natl. Cancer Inst., 81: 1874, 1989.
56. Cowan, J. M., Beckett, M. A., Tarbell, N. J. and Weichselbaum, R. R.: Monosomy 12p in a radiation-induced germ cell tumor. Genes, Chrom. Cancer, 2: 186, 1990.
57. Motzer, R. J., Rodriguez, E., Reuter, V. E., Samaniego, F., Dmitrovsky, E., Bajorin, D. F., Pfister, D. G., Parsa, N. Z., Chaganti, R. S. and Bosl, G. J.: Genetic analysis aids in the diagnosis of patients with midline carcinomas of uncertain histologies. J. Natl. Cancer Inst., 83: 341, 1991.
58. Delozier-Blanchet, C. D., Walt, H., Engel, E. and Vaugnat, P.: Cytogenetic studies of human testicular germ cell tumours. Int. J. Androl., 10: 69, 1987.
59. Geurts van Kessel, A., Suijkerbuijk, R. F., Sinke, R. J., Looijenga, L., Oosterhuis, J. W. and de Jong, B.: Molecular cytogenetics of human germ cell tumors: i(12p) and related chromosomal anomalies. Eur. Urol., 23: 23, 1993.
60. Geurts van Kessel, A., van Drunen, E., de Jong, B., Oosterhuis, J. W., Langeveld, A. and Mulder, M. P.: Chromosome 12q heterozygosity is retained in i(12p)-positive testicular germ cell tumor cells. Cancer Genet. Cytogenet., 40: 129, 1989.
61. Sinke, R. J., Suijkerbuijk, R. F., de Jong, B., Oosterhuis, J. W. and Geurts van Kessel, A.: Uniparental origin of i(12p) in human germ cell tumors. Genes, Chrom. Cancer, 6: 161, 1993.
62. Mukherjee, A. B., Murty, V. V., Rodriguez, E., Reuter, V. E., Bosl, G. J. and Chaganti, R. S.: Detection and analysis of origin of i(12p), a diagnostic marker of human male germ cell tumors, by fluorescence in situ hybridization. Genes, Chrom. Cancer, 3: 300, 1991.
63. Atkin, N. B. and Baker, M. C.: High chromosome numbers of testicular germ cell tumours. Cancer Genet. Cytogenet., 88: 90, 1995.
64. de Jong, B., Oosterhuis, J. W., Castedo, S. M., Vos, A. and te Meerman, G. J.: Pathogenesis of adult testicular germ cell tumors. A cytogenetic model. Cancer Genet. Cytogenet., 48: 143, 1990.
65. Klinger, H. P. and Kaelbling, M.: Suppression of tumorigenicity in somatic cell hybrids. IV. Chromosomes of normal human cells associated with suppression of tumorigenicity in hybrids with D98AH2 carcinoma cells. Cytogenet. Cell Genet., 42: 225, 1986.
66. Harris, H.: Suppression of malignancy in hybrid cells: the mechanism. J. Cell Sci., 79: 83, 1985.
67. Knudson, A. G., Jr.: Hereditary cancer, oncogenes, and antion-cogenes. Cancer Res., 45: 1437, 1985.
68. Stanbridge, E. J., Flandermeyer, R. R., Daniels, D. W. and Nelson-Rees, W. A.: Specific chromosome loss associated with the expression of tumorigenicity in human cell hybrids. Somatic Cell Genet., 7: 699, 1981.
69. Stock, C., Ambros, I. M., Zoubek, A., Gadner, H. and Ambros, P. F.: Detection of numeric and structural chromosome abnormalities in pediatric germ cell tumors by means of interphase cytogenetics. Cancer Genet. Cytogenet., 77: 196, abstract, 1994.
70. Bosl, G. J., Ilson, D. H., Rodriguez, E., Motzer, R. J., Reuter, V. E. and Chaganti, R. S.: Clinical relevance of the i(12p) marker chromosome in germ cell tumors. J. Natl. Cancer Inst., 86: 349, 1994.
71. Berger, C. S., Pennington, R. D., Dobbs, R., Haddad, F. S. and Sandberg, A. A.: Cytogenetic aspects of germ cell tumors of the testis. Cancer Genet. Cytogenet., 38: 147, 1987.
72. Walt, H., Arrenbrecht, S., Delozier-Blanchet, C. D., Keller, P. J., Nauer, R. and Hedinger, C. E.: A human testicular germ cell tumor with borderline histology between seminoma and embryonal carcinoma secreted beta-human chorionic gonadotropin and alpha-fetoprotein only as a xenograft. Cancer, 58: 139, 1986.
73. de Graaff, W. E., Oosterhuis, J. W., de Jong, B., Dam, A., van Putten, W. L., Castedo, S. M., Sleijfer, D. T. and Schraffordt Koops, H.: Ploidy of testicular carcinoma in situ. Lab. Invest., 66: 166, 1992.
74. Oosterhuis, J. W. and Looijenga, L. H.: The biology of human germ cell tumours: retrospective speculations and new perspectives. Eur. Urol., 23: 245, 1993.
75. Pierce, G. B. and Abell, M. R.: Embryonal carcinoma of the testis. Path. Ann., 5: 27, 1970.
76. Nochomovitz, L. E. and Rosai, J.: Current concepts on the histogenesis, pathology, and immunohistochemistry of germ cell tumors of the testis. Path. Ann., 13: 327, 1978.
77. Ewing, J.: Teratoma testis and its derivates. Surg., Gynec. & Obst., 12: 230, 1911.
78. Damjanov, I.: Is seminoma a relative or a precursor of embryonal carcinoma? Lab. Invest., 60: 1, 1989.
79. Friedman, N. B.: Comparative morphogenesis of extragenital and gonadal teratoid tumors. Cancer, 4: 265, 1951.
80. Mann, J. R.: The United Kingdom Children's Cancer Study Group yolk sac tumour studies. Adv. Biosci., 55: 169, 1986.
81. Gonzalez-Cruzzi, F.: Testicular and paratesticular tumors of childhood. In: Pathology of the Testis and its Adnexa. Edited by A. Talerman and L. M. Roth. New York: Churchill Livingstone, pp. 131-153, 1986.
82. Sesterhenn, I. A., Mostofi, F. K. and Davis, C. J., Jr.: Testicular tumours in infants and children. Adv. Biosci., 55: 173, 1986.
83. Jacobsen, G. K., Henriksen, O. B. and von der Maase, H.: Carcinoma in situ of testicular tissue adjacent to malignant germ-cell tumors: a study of 105 cases. Cancer, 47: 2660, 1981.
84. Oosterhuis, J. W., Castedo, S. M., de Jong, B., Seruca, R., Buist, J., Schraffordt Koops, H. and Leeuw, J. A.: Karyotyping and DNA flow cytometry of an orchidoblastoma. Cancer Genet. Cytogenet., 36: 7, 1988.
85. Trask, B.: Fluorescence in situ hybridization: applications in cytogenetics and gene mapping. Trends Genet., 7: 149, 1991.
86. Pinkel, D., Landegent, J., Collins, C., Fuscoe, J., Segraves, R., Lucas, J. and Gray, J.: Fluorescence in situ hybridization with human chromosome-specific libraries: detection of trisomy 21 and translocations of chromosome 4. Proc. Natl. Acad. Sci., 85: 9138, 1988.
87. Nederlof, P. M., van der Flier, S., Raap, A. K., Tanke, H. J., Ploem, J. S. and van der Ploeg, M.: Multiple fluorescence in situ hybridization. Cytometry, 11: 126, 1990.
88. Dauwerse, J. G., Wiegant, J., Raap, A. K., Breuning, M. H. and van Ommen, G. J.: Multiple colors by fluorescence in situ hybridization using radio-labelled DNA probes create a molecular karyotype. Hum. Mol. Genet., 1: 593, 1992.
89. Lengauer, C., Speicher, M. R., Popp, S., Jauch, A., Taniwaki, M., Nagaraja, R., Riethman, H. C., Donis-Keller, H., D'Urso, M., Schlessinger, D. and Cremer, T.: Chromosomal bar codes produced by multicolor fluorescence in situ hybridization with multiple YAC clones and whole chromosome painting probes. Hum. Mol. Genet., 2: 505, 1993.
90. Popp, S., Jauch, A., Schindler, D., Speicher, M. R., Lengauer, C., Donis-Keller, H., Riethman, H. C. and Cremer, T.: A strategy for the characterization of minute chromosome arrangements using multiple color fluorescence in situ hybridization with chromosome-specific DNA libraries and YAC clones. Hum. Genet., 92: 527, 1993.
91. Suijkerbuijk, R. F., Sinke, R. J., Weghuis, D. E., Roque, L., Forus, A., Stellink, F., Siepman, A., van de Kaa, C., Soares, J. and Geurts van Kessel, A.: Amplification of chromosome subregion 12p11.2-p12.1 in a metastasis of an i(12p)-negative seminoma: relationship to tumor progression? Cancer Genet. Cytogenet., 78: 145, 1994.
92. Van der Riet-Fox, M., Retief, A. E. and van Niekerk, W. A.: Chromosome changes in 17 human neoplasms studied with banding. Cancer, 44: 2108, 1979.
93. Rodriguez, E., Rao, P. H., Ladanyi, M., Altorki, N., Abino, A. P., Kelsen, D. P., Jhanwar, S. C. and Chaganti, R. S.: 11p13-15 is a specific region of chromosomal rearrangement in gastric and esophageal adenocarcinomas. Cancer Res., 50: 6410, 1990.
94. Sreekantaiah, C., Rao, U. N. and Sandberg, A. A.: Complex karyotypic aberrations, including i(12p), in malignant mixed mullerian tumor of the uterus. Cancer Genet. Cytogenet., 60: 78, 1992.
95. Rodrigues, N. R., Rowan, A., Smith, M. E., Kerr, I. B., Bodner, W. F., Gannon, J. V. and Lane, D. P.: p53 mutations in colorectal cancer. Proc. Natl. Acad. Sci., 87: 7555, 1990.
96. Suijkerbuijk, R. F., van der Veen, A. Y., van Echten, J., Buys, C. H., de Jong, B., Oosterhuis, J. W., Warburton, D. A., Cassiman, J. J., Schonk, D. and Geurts van Kessel, A.: Demonstration of the genuine iso-12p character of the standard marker chromosome of testicular germ cell tumors and identification of further chromosome 12 aberrations by competitive in situ hybridization. Amer. J. Hum. Genet., 48: 269, 1991.
97. Suijkerbuijk, R. F., Looijenga, L., de Jong, B., Oosterhuis, J. W., Cassiman, J. J. and Geurts van Kessel, A.: Verification of isochromosome 12p and identification of other chromosome 12 aberrations in human germ cell tumors by bicolor double fluorescence in situ hybridization. Cancer Genet. Cytogenet., 63: 8, 1992.
98. Hamers, A., de Jong, B., Suijkerbuijk, R. F., Geurts van Kessel, A., Oosterhuis, J. W., van Echten, J., Evers, J. and Bosman, F.: A 46,XY female with mixed gonadal dysgenesis and a 48,XY, +7, +i(12p) chromosome pattern in a primary gonadal tumor. Cancer Genet. Cytogenet., 57: 219, 1991.
99. Speleman, F., Laureys, G., Benoit, Y., Cuvelier, C., Suijkerbuijk, R. F. and de Jong, B.: i(12p) in a near diploid mature ovarian teratoma. Letter to the Editor. Cancer Genet. Cytogenet., 60: 216, 1992.
100. Aly, M. S., Dal Cin, P., Jiskoot, P., Deneffe, G., Marynen, P. and Van den Berghe, H.: Competitive in situ hybridization in a mediastinal germ cell tumor. Cancer Genet. Cytogenet., 73: 53, 1994.
101. De Bruin, T. W., Slater, R. M., Defferreri, R., Geurts van Kessel, A., Suijkerbuijk, R. F., Jansen, G., de Jong, B. and Oosterhuis, J. W.: Isochromosome (12p) positive pineal germ cell tumor. Cancer Res., 54: 1542, 1994.
102. Peltomäki, P., Lothe, R. A., Børresen, A. L., Fossä, S. D., Brøgger, A. and de la Chapelle, A.: Chromosome 12 in human testicular cancer: dosage changes and their parental origin. Cancer Genet. Cytogenet., 64: 21, 1992.
103. Castedo, S. M., de Jong, B., Oosterhuis, J. W., Seruca, R., Idenburg, V. J., Buist, J. and Sleijfer, D. T.: i(12p)-negative testicular germ cell tumors. A different group? Cancer Genet. Cytogenet., 35: 171, 1988.
104. Castedo, S. M. M. J., Oosterhuis, J. W. and de Jong, B.: Cytogenetic studies of testicular germ cell tumors: pathogenetic relevance. Pathobiology of human germ cell neoplasia. Recent Results Cancer Res., 123: 101, 1991.
105. Sinke, R. J., Suijkerbuijk, R. F., Herbergs, J., Janssen, H., Cassiman, J. J. and Geurts van Kessel, A.: Generation of a panel of somatic cell hybrids containing fragments of human chromosome 12p by X-ray irradiation and cell fusion. Genomics, 12: 206, 1992.
106. Kallioniemi, A, Kallioniemi, O., Sudar, D., Rutovitz, D., Gray, J. W., Waldman, F. and Pinkel, D.: Comparative genomic hybridization of molecular cytogenetic analysis of solid tumors. Science, 258: 818, 1992.
107. Du Manoir, S., Speicher, M. R., Joos, S., Schröck, E., Popp, S., Döhner, H., Kovacs, G., Robert-Nicoud, M., Lichter, P. and Cremer, T.: Detection of complete and partial chromosome gains and losses by comparative genomic in situ hybridization. Hum. Genet., 90: 590, 1993.
108. Brison, O.: Gene amplification and tumor progression. Biochem. Biophys. Acta, 1155: 25, 1993.
109. Moseley, J. M., Kubota, M., Diefenbach-Jagger, H., Wettenhall, R. E., Kemp, B. E., Suva, L. J., Rodda, C. P., Ebeling, P. R., Hudson, P. J., Zajac, J. D. and Martin, T. J.: Parathyroid hormone-related protein purified from a human lung cancer cell line. Proc. Natl. Acad. Sci., 84: 5048, 1987.
110. Stewart, A. F., Wu, T., Goumas, D., Burtis, W. J. and Broadus, A. F.: N-terminal amino acid sequence of two novel tumor-derived adenylate cyclase-stimulating proteins: identification of parathyroid hormone-like and parathyroid hormone-unlike domains. Biochem. Biophys. Res. Comm., 146: 672, 1987.
111. Pausova, Z., Morgan, K., Fujiwara, M., Bourdon, J., Goltzman, D. and Hendy, G. N.: Molecular characterization of an intragenic minisatellite (VNTR) polymorphism in the human parathyroid hormone related peptide in chromosome region 12p12.1-p11.2. Genomics, 17: 243, 1993.
112. Martin, T. J., Allan, E. H., Caple, I. W., Care, A. D., Danks, J. A., Diefenbach-Jagger, H., Ebeling, P. R., Gillespie, M. T., Hammonds, G., Heath, J. A., Hudson, P. J., Kemp, B. E., Kubota, M., Kurkreja, S. C., Mosely, J. M., Ng, K. W., Raisz, L. G., Rodda, C. P., Simmons, H. A., Suva, L. J., Wettenhall, R. E. and Wood, W. I.: Parathyroid hormone-related protein: isolation, molecular cloning, and mechanisms of action. Recent Prog. Horm. Res., 45: 467, 1989.
113. Shimogaki, H., Kitazawa, S., Maeda, S. and Kamidono, S.: Variable expression of hst-1, int-1, and parathyroid hormone-related protein in different histological types of human testicular germ cell tumors. Cancer J., 6: 81, 1993.
114. Rudduck, C., Duncan, L., Center, R. and Garson, O. M.: Coamplification of the gene for parathyroid hormone-related protein (PTHRP) and KRAS2 in a human lung cancer cell line. Genes, Chrom. Cancer, 7: 213, 1993.
115. Korn, M. and Looijenga, L.: Personal communication.
116. Willard, H. F.: Molecular cytogenetics of centromeres of human chromosomes. Chrom. Today, vol. 10, 1990.
117. Seemayer, T. A. and Cavenee, W. K.: Molecular mechanisms of oncogenesis. Lab. Invest., 60: 585, 1989.
118. Darlington, C. D.: Misdivision and the genetics of the centromere. J. Genet., 37: 341, 1939.
119. de la Chapelle, A.: How do human isochromosomes arise? Cancer Genet. Cytogenet., 5: 173, 1982.
120. Fraccaro, M., Ikkos, D., Lindsten, J., Luft, R. and Kaijser, K.: A new type of chromosomal abnormality in gonadal dysgenesis. Lancet, 2: 1144, 1960.
121. Caspersson, T., Lindsten, J. and Zech, L.: The nature of structural X chromosome aberrations in Turner's syndrome as revealed by quinacrine mustard fluorescence analysis. Hereditas, 66: 287, 1970.
122. Sharp, C. B., Bedford, H. M. and Willard, H. F.: Pericentromeric structure of human X "isochromosomes": evidence for molecular heterogeneity. Hum. Genet., 85: 330, 1990.
123. Looijenga, L. H. J., Gillis, A. J. M., Hoekstra, J. W., de Jong, B., Sinke, R. J., Geurts van Kessel, A. and Oosterhuis, J. W.: Involvement of chromosomes 12 and 22 in testicular germ cell tumor of adults. Genes, Chrom. Cancer, in press.
124. Botstein, D., White, R. L., Skolnick, M. and Davis, R. W.: Construction of a genetic map in man using restriction fragment length polymorphisms. Amer. J. Hum. Genet., 32: 314, 1980.
125. Nakamura, Y., Leppert, M., O'Connell, P., Wolff, R., Holm, T., Culver, M., Martin, C., Fujimoto, E., Hoff, M., Kumlin, E. and White, R.: Variable number of tandem repeat (VNTR) markers for human gene mapping. Science, 235: 1616, 1987.
126. Hunter, T.: Cooperation between oncogenes. Cell, 64: 249, 1991.
127. Green, A. R. and Wyke, J. A.: Anti-oncogenes. A subset of regulatory genes involved in carcinogenesis? Lancet, 2: 475, 1985.
128. Knudson, A. G.: All in the (cancer) family. Nature Genet., 5: 103, 1993.
129. Knudson, A. G., Jr.: Genetics of human cancer. J. Cell Physiol., suppl., 4: 7, 1986.
130. Friend, S. H., Horowitz, J. M., Gerber, M. R., Wang, X. F., Bogenmann, E., Li, F. P. and Weinberg, R. A.: Deletions of a DNA sequence in retinoblastomas and mesenchymal tumors: organization of the sequence and its encoded protein. Proc. Natl. Acad. Sci., 84: 9059, 1987.
131. Call, K. M., Glaser, T., Ito, C. Y., Buckler, A. J., Pelletier, J., Haber, D. A., Rose, E. A., Kral, A., Yeger, H., Lewis, W. H., Jones, C. and Housman, D.: Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms' tumor locus. Cell, 60: 509, 1990.
132. Gessler, M., Poustka, A., Cavenee, W., Neve, R. L., Orkin, S. H. and Bruns, G. A.: Homozygous deletion in Wilms tumours of a zinc-finger gene identified by chromosome jumping. Nature, 343: 774, 1990.
133. Malkin, D., Li, F. P., Strong, L. C., Fraumeni, J. F., Jr., Nelson, C. E., Kim, D., Kassel, J., Gryka, M. A., Bischoff, F. Z., Tainsky, M. A. and Friend, S. H.: Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science, 250: 1233, 1990.
134. Wang, N., Trend, B., Bronson, D. L. and Fraley, E. E.: Nonrandom abnormalities in chromosome 1 in human testicular cancers. Cancer Res., 40: 796, 1980.
135. Parrington, J. M., West, L. F. and Povey, S.: Chromosome changes in germ cell tumors. In: Proceedings of the Second Germ Cell Conference. Edited by W. G. Jones, A. Milford Ward and C. K. Anderson. Elmsford, New York: Pergamon Press, pp. 61-67, 1985.
136. Parrington, J. M., West, L. F. and Povey, S.: Loss of heterozygosity in hypotriploid cell cultures from testicular tumours. Hum. Genet., 77: 269, 1987.
137. Parrington, J. M. and West, L. F.: Loss of chromosome and enzyme markers in cultures from testicular tumours. Clin. Genet., 27: 326, 1985.
138. Mathew, S., Murty, V. V., Bosl, G. J. and Chaganti, R. S.: Loss of heterozygosity identifies multiple sites of allelic deletions on chromosome 1 in human male germ cell tumors. Cancer Res., 54: 6265, 1994.
139. Murty, V. V. V. S., Dmitrovsky, F., Bosl, G. J. and Chaganti, R. S. K.: Nonrandom chromosome abnormalities in testicular and ovarian germ cell lines. Cancer Genet. Cytogenet., 50: 67, 1990.
140. Murty, V. V., Li, R. G., Mathew, S., Reuter, V. E., Bronson, D. L., Bosl, G. J. and Chaganti, R. S.: Replication error-type genetic instability at 1q42-43 in human male germ cell tumors. Cancer Res., 54: 3983, 1994.
141. Radice, P., Pierotti, M. A., Lacerenza, S., Mondini, P., Radice, M. T., Pilotti, S. and Della Porta, G.: Loss of heterozygosity in human germinal tumors. Cytogenet. Cell Genet., 52: 72, 1989.
142. Peltomäki, P., Halme, A. and de la Chapelle, A.: Human testicular cancer. Changes in autosomal dosage. Cancer Genet. Cytogenet., 48: 1, 1990.
143. Murty, V. V., Houldsworth, J., Baldwin, S., Reuter, V., Hunziker, W., Besmer, P., Bosl, G. and Chaganti, R, S. K.: Allelic deletions in the long arm of chromosome 12 identify candidate tumor suppressor genes in male germ cell tumors. Proc. Natl. Acad. Sci., 89: 11006, 1992.
144. Lothe, R. A., Fosså, S. D., Stenwig, A. E., Nakamura, Y., White, R., Børresen, A. L. and Brogger, A.: Loss of 3p or 11p alleles is associated with testicular cancer tumors. Genomics, 5: 134, 1989.
145. Lothe, R. A., Hastie, N., Heimdal, K., Fosså, S. D., Stenwig, A. E. and Børresen, A.: Frequent loss of 11p13 and 11p15 loci in male germ cell tumors. Genes Chrom. Cancer, 7: 96, 1993.
146. Slater, R. M. and Mannens, M. M.: Cytogenetics and molecular genetics of Wilms' tumor in childhood. Cancer Genet. Cytogenet., 61: 111, 1992.
147. Viel, A., Giannini, F., Tumiotto, L., Sopracordevole, F., Visentin, M. C. and Boiocchi, M.: Chromosomal localisation of two putative 11p oncosuppressor genes involved in human ovarian tumours. Brit. J. Cancer, 66: 1030, 1992.
148. Vandamme, B., Lissens, W., Amfo, K., De Sutter, P., Bourgain, C., Vamos, E. and De Grève, J.: Deletion of chromosome 11p13-11p15.5 sequences in invasive human ovarian cancer is a subclonal progression factor. Cancer Res., 52: 6646, 1992.
149. Bonetta, L., Kuehn, S. E., Huang, A., Law, D. J., Kalikin, L. M., Koi, M., Reeve, A. E., Brownstein, B. H., Yeger, H., Williams, B. R. and Feinberg, A. P.: Wilms tumor locus on 11p13 defined by multiple CpG island-associated transcripts. Science, 250: 994, 1990.
150. Pelletier, J., Bruening, W., Li, F. P., Haber, D. A., Glaser, T. and Housman, D. E.: WT1 mutations contribute to abnormal genital system development and hereditary Wilms' tumour. Nature, 353: 431, 1991.
151. Pelletier, J., Bruening, W., Kashtan, C. E., Mauer, S. M., Manivel, J. C., Striegel, J. E., Houghton, B. L., Haber, D. A. and Housman, D. E.: Germline mutations in the Wilms' tumor suppressor gene are associated with abnormal urogenital development in Denys-Drash syndrome. Cell, 67: 437, 1991.
152. Pelletier, J., Schalling, M., Buckler, A. J., Rogers, A., Haber, D. A. and Housman, D.: Expression of the Wilms' tumor gene WT1 in the murine urogenital system. Genes Dev., 5: 1345, 1991.
153. Armstrong, J. F., Pritchard-Jones, K., Bickmore, W. A., Hastie, N. D. and Bard, J. B.: The expression of the Wilms tumour gene, WT1, in the developing mammalian embryo. Mech. Dev., 40: 85, 1992.
154. Bruening, W., Bardeesy, N., Silverman, B. L., Cohn, R. A., Machin, G. A., Aronson, A. J., Housman, D. and Pelletier, J.: Germline intronic and exonic mutations in the Wilms' tumor gene (WT1) affecting urogenital development. Nature Genet., 1: 144, 1992.
155. Pritchard-Jones, K., Fleming, S., Davidson, D., Bickmore, W., Porteous, D., Gosden, C., Bard, J., Buckler, A., Pelletier, J., Housman, D., van Heyningen, V. and Hastie, N.: The candidate Wilms' tumour gene is involved in genitourinary development. Nature, 346: 194, 1990.
156. Looijenga, L. H. J., Abraham, M., Gillis, A. J. M., Saunders, G. F. and Oosterhuis, J. W.: Testicular germ cell tumors of adults show deletions of chromosomal bands 11p13 and 11p15.5, but no abnormalities within the zinc-finger regions and exons 2 and 6 of the Wilms' tumor 1 gene. Genes, Chrom. Cancer, 9: 153, 1993.
157. Heimdal, K. R., Lothe, R. A., Fosså, S. D. and Børresen, A. L.: Association studies of a polymorphism in the Wilms' tumor 1 locus in Norwegian patients with testicular cancer. Int. J. Cancer, 58: 523, 1994.
158. Smith, R. C. and Rukstalis, D. B.: Frequent loss of heterozygosity at 11P loci in testicular cancer. J. Urol., 153: 1684, 1995.
159. Peng, H. Q., Bailey, D., Bronson, D., Goss, P. E. and Hogg, D.: Loss of heterozygosity of tumor suppressor genes in testis cancer. Cancer Res., 55: 2871, 1995.
160. Murty, V. V., Li, R. G., Houldsworth, J., Bronson, D. L., Reuter, V. E., Bosl, G. J. and Chaganti, R. S.: Frequent allelic deletions and loss of expression characterize the DCC gene in male germ cell tumors. Oncogene, 9: 3227, 1994.
161. Rukstalis, D. B., Bubbley, G. J., Donahue, J. P., Richie, J. P., Seidman, J. G. and DeWolf, W. C.: Regional loss of chromosome 6 in two urological malignancies. Cancer Res., 49: 5087, 1989.
162. Goldfischer, E. R., Rinker-Schaeffer, C. W., Rukstalis, D. B. and Stadler, W.: Loss of heterozygosity (LOH) on the 9p chromosomal arm in testicular cancer. J. Urol., part 2, 153: 311A, abstract 332, 1995.
163. Strohmeyer, T., Reissmann, P., Cordon-Cardo, C., Hartmann, M., Ackermann, R. and Slamon, D.: Correlation between retinoblastoma gene expression and differentiation in human testicular tumors. Proc. Natl. Acad. Sci., 88: 6662, 1991.
164. DeCaprio, J. A., Ludlow, J. W., Figge, J., Shew, J. Y., Huang, C. M., Lee, W. H., Marsilio, E., Paucha, E. and Livingston, D. M.: SV40 large tumor antigen forms a specific complex with the product of the retinoblastoma susceptibility gene. Cell, 54: 275, 1988.
165. Lee, W. H., Bookstein, R., Hong, F., Young, L. J., Shew, J. Y. and Lee, E. Y.: Human neuroblastoma susceptibility gene: cloning, identification, and sequence. Science, 235: 1394, 1987.
166. Friend, S. H., Bernards, R., Rogelj, S., Weinburg, R. A., Rapaport, J. M., Albert, D. M. and Dryja, T. P.: A human DNA segment with properties of the
167. Fung, Y. K., Murphree, A. L., T'Ang, A., Qian, J., Hinrichs, S. H. and Benedict, W. F.: Structural evidence for the authenticity of the human retinoblastoma gene. Science, 236: 1657, 1987.
168. Hansen, M. F., Koufos, A., Gallie, B. L., Phillips, R. A., Fodstad, O., Brøgger, A., Gedde-Dahl, T. and Cavenee, W. K.: Osteosarcoma and retinoblastoma: a shared chromosomal mechanism revealing recessive predisposition. Proc. Natl. Acad. Sci., 82: 6216, 1985.
169. Weichselbaum, R. R., Beckett, M. and Diamond, A.: Some retinoblastomas, osteosarcomas, and soft tissue sarcomas may share a common etiology. Proc. Natl. Acad. Sci., 85: 2106, 1988.
170. Reissmann, P. T., Simon, M. A., Lee, W. H. and Slamon, D. J.: Studies of the retinoblastoma gene in human sarcomas. Oncogene, 4: 839, 1989.
171. Cance, W. G., Brennan, M. F., Dudas, M. E., Huang, C. M. and Cordon-Cardo, C.: Altered expression of the retinoblastoma gene product in human sarcomas. New Engl. J. Med., 323: 1457, 1990.
172. Harbour, J. W., Lai, S. L., Whang-Peng, J., Gazdar, A. F., Minna, J. D. and Kaye, F. J.: Abnormalities in structure and expression of the human retinoblastoma gene in SCLC. Science, 241: 353, 1988.
173. Lee, E. Y., To, H., Shew, J. Y., Bookstein, R., Scully, P. and Lee, W. H.: Inactivation of the retinoblastoma susceptibility gene in human breast cancers. Science, 241: 218, 1988.
174. Varley, J. M., Armour, J., Swallow, J. E., Jeffreys, A. J., Ponder, B. A. J., T'Ang, A., Fung, Y. K., Brammar, W. J. and Walker, R. A.: The retinoblastoma gene is frequently altered leading to loss of expression in primary breast tumours. Oncogene, 4: 725, 1989.
175. Horowitz, J. M., Yandell, D. W., Park, S. H., Canning, S., Whyte, P., Buchkovich, K., Harlow, E., Weinberg, R. A. and Dryja, T. P.: Point mutational inactivation of the retinoblastoma antioncogene. Science, 243: 937, 1989.
176. Sidransky, D., Von Eschenbach, A., Tsai, Y. C., Jones, P., Summerhayes, I., Marshall, F., Paul, M., Green, P., Hamilton, S. R., Frost, P. and Vogelstein, B.: Identification of p53 gene mutations in bladder cancers and urine samples. Science, 252: 706, 1991.
177. Nigro, J. M., Baker, S. J., Preisinger, A. C., Jessup, J. M., Hostetter, R., Cleary, K., Bigner, S. H., Davidson, N., Baylin, S., Devilee, P., Glover, T., Collins, F. S., Weston, A., Modali, R., Harris, C. C. and Vogelstein, B.: Mutations in the p53 gene occur in diverse human tumour types. Nature, 342: 705, 1989.
178. Catoretti, G., Rilke, F., Andreola, S., D'Amato, L. and Delia, D.: P53 expression in breast cancer. Int. J. Cancer, 41: 178, 1988.
179. Iggo, R., Gatter, K., Bartek, J., Lane, D. and Harris, A. L.: Increased expression of mutant forms of p53 oncogene in primary lung cancer. Lancet, 335: 675, 1990.
180. Wright, C., Mellon, K., Johnston, P., Lane, D. P., Harris, A. L., Horne, C. H. and Neal, D. E.: Expression of mutant p53, a c-erbB-2 and the epidermal growth factor receptor in transitional cell carcinoma of the human urinary bladder. Brit. J. Cancer, 63: 967, 1991.
181. Varley, J. M., Brammar, W. J., Lane, D. P., Swallow, J. E., Dolan, C. and Walker, R. A.: Loss of chromosome 17p13 sequences and mutation of p53 in human breast carcinomas. Oncogene, 6: 413, 1991.
182. Crawford, L. V., Pim, D. C., Gurney, E. G., Goodfellow, P. and Taylor-Papadimitrou, J.: Detection of a common feature in several human tumor cell lines - a 53,000-dalton protein. Proc. Natl. Acad. Sci., 78: 41, 1981.
183. Klein, N., Vignaud, J. M., Sadmi, M., Plenat, F., Borelly, J., Duprez, A., Martinet, Y. and Martinet, N.: Squamous metaplasia expression of proto-oncogenes and P 53 in lung cancer patients. Lab. Invest., 68: 26, 1993.
184. Bártek, J., Bártková, J., Vojtěsek, B., Stasková, Z., Lukás, J., Rejthar, A., Kovařík, J., Midgley, C. A., Gannon, J. V. and Lane, D. P.: Aberrant expression of the p53 oncoprotein is a common feature of a wide spectrum of human malignancies. Oncogene, 6: 1699, 1991.
185. Bártková, J., Bártek, J., Lukás, J., Vojtěsek, B., Stasková, Z., Rejthar, A., Kovařík, J., Midgley, C. A. and Lane, D. P.: p53 protein alterations in human testicular cancer including preinvasive intratubular germ-cell neoplasia. Int. J. Cancer, 49: 196, 1991.
186. Kuczyk, M. A., Serth, J., Allhoff, E. P., Thon, W. and Jonas, U.: P53 mutant gene expression in archival material of mature teratoma of the testis. J. Urol., part 2, 149:310A, abstract 391, 1993.
187. Schultz, D. S., Linden, M. D. and Kormann, H. J.: Biology of disease: molecular mechanisms of oncogenesis. Lab. Invest., 60: 585, 1989.
188. Ulbright, T., Orazi, A., DeRiese, W., Messemer, J. and Eble, J.: The relationship of p53, PCNA, and S-phase in nonseminomatous germ cell tumors. Lab. Invest., 68: 71A, abstract 404, 1993.
189. Lewis, D. J., Sesterhenn, I. A., McCarthy, W. F. and Moul, J. W.: Immunohistochemical expression of p53 tumor suppressor gene protein in adult germ cell testis tumors: clinical correlation in stage I disease. J. Urol., 152: 418, 1994.
190. Schenkman, N. S., Sesterhenn, I. A., Washington, L., Tong, Y. A., Weghorst, C. M., Buzard, G. S., Srivastava, S. and Moul, J. W.: Increased p53 protein does not correlate to p53 gene mutations in microdissected human testicular germ cell tumors. J. Urol., 154: 617, 1995.
191. DeRiese, W. T. W., Orazi, A., Foster, R. S., Donohue, J. P. and Messemer, J. E.: The clinical relevance of p 53 expression in early stage, nonseminomatous germ cell tumor. J. Urol., part 2, 149: 311A, abstract 392, 1993.
192. Strohmeyer, T. G., Fleishhacker, M., Imai, Y., Slamon, D. J. and Koeffler, H. P.: Status of the p53 tumor suppressor gene and the MDM-2 gene in human testicular tumors. J. Urol., part 2, 149: 311A, abstract 393, 1993.
193. Riou, G., Barrois, M., Prost, S., Terrier, M. J., Theodore, C. and Levine, A. J.: The p53 and mdm-2 genes in human testicular germ-cell tumors. Molec. Carcinogenesis, 12: 124, 1995.
194. Rodenhuis, S.: ras and human tumors. Sem. Cancer Biol., 3: 241, 1992.
195. McCormick, F.: Signal transduction. How receptors turn ras on. Nature, 363: 15, 1993.
196. Kumar, R., Sukumar, S. and Barbacid, M.: Activation of ras oncogenes preceding the onset of neoplasia. Science, 248:1101, 1990.
197. Wang, L. C., Vass, W., Gao, C. L. and Chang, K. S.: Amplification and enhanced expression of the c-Ki-ras2 protooncogene in human embryonal carcinomas. Cancer Res., 47:4192, 1987.
198. Peltomäki, P., Alfthan, O. and de la Chapelle, A.: Oncogenes in human testicular cancer: DNA and RNA studies. Brit. J. Cancer, 63: 851, 1991.
199. Mulder, M. P., Keijzer, W., Verkerk, A., Boot, A. J., Prins, M. E., Splinter, T. A. and Bos, J. L.: Activated ras genes in human seminoma: evidence for tumor heterogeneity. Oncogene, 4: 1345, 1989.
200. Dmitrovsky, E., Murty, V. V., Moy, D., Miller, W. H., Jr., Nanus, D., Albino, A. P., Samaniego, F., Bosl, G. and Chaganti, R. S.: Isochromosome 12p in non-seminoma cell lines: karyotypic amplification of c-ki-ras2 without point-mutational activation. Oncogene, 5: 543, 1990.
201. Ganguly, S., Murty, V. V., Samaniego, F., Reuter, V. E., Bosl, G. J. and Chaganti, R. S.: Detection of preferential NRAS mutations in human male germ cell tumors by the polymerase chain reaction. Genes, Chrom. Cancer, 1: 228, 1990.
202. Tesch, H., Fürbass, R., Casper, J., Lyons, J., Bartram, C. R., Schmoll, H. J. and Bronson, D. L.: Cellular oncogenes in human teratocarcinoma cell lines. Int. J. Androl., 13: 377, 1990.
203. Moul, J. W., Theune, S. M. and Chang, E. H.: Detection of ras mutations in archival testicular germ cell tumors by polymerase chain reaction and oligonucleotide hybridization. Genes, Chrom. Cancer, 5: 109, 1992.
204. Ridanpää, M., Lothe, R. A., Onfelt, A., Fosså, S., Børessen, A. L. and Husgafvel-Pusiainen, K.: K-ras oncogene codon 12 mutations in testicular cancer. Environ. Health Perspect., suppl. 3, 101: 185, 1993.
205. Olie, R. A., Looijenga, L. H., Boerrigter, L., Top, B., Rodenhuis, S., Langeveld, A., Mulder, M. P. and Oosterhuis, J. W.: N- and KRAS mutations in primary testicular germ cell tumors: incidence and possible biological implications. Genes, Chrom. Cancer, 12: 110, 1995.
206. Sehrt, J., Pietsch, T., Schöffski, P., Bokemeyer, C., Kuczyk, M. A., Schmooll, H. J. and Jonas, U.: A possible role for stem cell factor (SCF) and its receptor C-kit in malignant germ cell tumors. Proc. Amer. Ass. Cancer Res., 35: 43, abstract, 1994.
207. Shuin, T., Misaki, H., Kubota, Y., Yao, M. and Hosaka, M.: Differential expression of protooncogenes in human germ cell tumors of the testis. Cancer, 73: 1721, 1994.
208. Feinberg, A. P.: Genomic imprinting and gene activation in cancer. Nature Genet., 4: 110, 1993.
209. Crouse, H.: The controlling element in sex chromosome behavior in Sciara. Genetics, 45: 1429, 1960.
210. Brandeis, M., Kafri, T., Ariel, M., Chaillet, J. R., McCarrey, J., Razin, A. and Cedar, H.: The ontogeny of allele-specific methylation associated with imprinted genes in the mouse. EMBO J., 12: 3669, 1993.
211. Ferguson-Smith, A. C., Sasaki, H., Cattenach, B. M. and Surani, M. A.: Parental-origin-specific epigenetic modification of the mouse H19 gene. Nature, 362: 751, 1993.
212. Sasaki, H., Jones, P. A., Chaillet, J. R., Ferguson-Smith, A. C., Barton, S. C., Reik, W. and Surani, M. A.: Parental imprinting: potentially active chromatin of the repressed maternal allele of the mouse insulin-like growth factor II (Igf2) gene. Genes Dev., 6: 1843, 1993.
213. Bartolomei, M. S., Webber, A. L., Brunkow, M. E. and Tilghman, S. M.: Epigenetic mechanisms underlying the imprinting of the mouse H19 gene. Genes Dev., 7: 1663, 1993.
214. Stöger, R., Kubička, P., Liu, C. G., Kafri, T., Razin, A., Cedar, H. and Barlow, D. P.: Maternal-specific methylation of the imprinted mouse igf2r locus identifies the expressed locus as carrying the imprinting signal. Cell, 73: 61, 1993.
215. Barlow, D. P.: Imprinting: a gamete's point of view. Trend. Genet., 10: 194, 1994.
216. Chaillet, J. R., Vogt, T. F., Beier, D. R. and Leder, P.: Parental-specific methylation of an imprinted transgene is established during gametogenesis and progressively changes during embryogenesis. Cell, 66: 77, 1991.
217. Bartolomei, M. S., Zemel, S. and Tilghman, S. M.: Parental imprinting of the mouse 1119 gene. Nature, 351: 153, 1991.
218. Barlow, D. P., Stöger, R., Herrmann, B. G., Saito, K. and Schweifer, N.: The mouse insulin-like growth factor type-2 receptor is imprinted and closely linked to the Tme locus. Nature, 349: 84, 1991.
219. DeChiara, T. M., Robertson, E. J. and Efstratiadis, A.: Parental imprinting of the mouse insulin-like growth factor II gene. Cell, 64: 849, 1991.
220. Rappolee, D. A., Sturm, K. S., Behrendtsen, O., Schultz, G. A., Pedersen, R. A. and Werb, Z.: Insulin-like growth factor II acts through an endogenous growth pathway regulated by imprinting in early mouse embryos. Genes Dev., 6: 939, 1992.
221. Leff, S. E., Brannan, C. I., Reed, M. L., Ozçelik, T., Francke, U., Copeland, N. G. and Jenkins, J. A.: Maternal imprinting of the mouse Snrpn gene and conserved linkage homology with the human Prader-Willi syndrome region. Nature Genet., 2: 259, 1992.
222. Solter, D.: Relevance of genomic imprinting to human disease. Curr. Opinion Biotechn., 3: 632, 1992.
223. Wilson, G. N., Hall, J. G. and de la Cruz, F.: Genomic imprinting: summary of an NICHD conference. Amer. J. Med. Genet., 46: 675, 1993.
224. Tycko, B.: Genomic imprinting: mechanism and role in human pathology. Amer. J. Path., 144: 431, 1994.
225. Ogawa, O., Eccles, M. R., Szeto, J., McNoe, L. A., Yun, K., Maw, M. A., Smith, P. J. and Reeve, A. E.: Relaxation of insulin-like growth factor II gene imprinting implicated in Wilms' tumour. Nature, 362: 749, 1993.
226. Rainier, S., Johnson, L. A., Dobry, C. J., Ping, A. J., Grundy, P. E. and Feinberg, A. P.: Relaxation of imprinted genes in human cancer. Nature, 362: 747, 1993.
227. Suzuki, H., Veda, R., Takahashi, T. and Takahashi, T.: Altered imprinting in lung cancer. Nature Genet., 6: 332, 1994.
228. Rachmilewitz, J., Goshen, R., Ariel, I., Schneider, T., de Groot, N. and Hochberg, A.: Parental imprinting of the human H19 gene. FEBS Lett., 309: 25, 1992.
229. Ohlsson, R., Nyström, A., Pfeifer-Ohlsson, S., Töhönen, V., Hedborg, F., Schofield, P., Flam, F. and Ekström, T. J.: IGF2 is parentally imprinted during human embryogenesis and in the Beckwith-Wiedemann syndrome. Nature Genet., 4: 94, 1993.
230. Zhang, Y. and Tycko, B.: Monoallelic expression of the human H19 gene. Nature Genet., 1: 40, 1992.
231. Giannoukakis, N., Deal, C., Paquette, J., Goodyear, C. G. and Polychronakos, C.: Parental genomic imprinting of the human IGF2 gene. Nature Genet., 4: 98, 1993.
232. van Gurp, R. J., Oosterhuis, J. W., Kalscheuer, V., Mariman, E. C. and Looijenga, L. H.: Biallelic expression of the H19 and IGF2 genes in human testicular germ cell tumors. J. Natl Cancer Inst., 86: 1070, 1994.
233. Friedman, N. B. and Moore, R. A.: Tumors of testis; report on 922 cases. Military Surg., 99: 573, 1946.
234. Dixon, F. J., Jr. and Moore, R. A.: Testicular tumors; clinicopathologic study. Cancer, 6: 427, 1953.
235. Skakkebaek, N. E. and Berthelsen, J. G.: Carcinoma in situ and orchiectomy. Letter to the Editor. Lancet, 2: 204, 1978.
236. Damjanov, I.: Pathobiology of human germ cell neoplasia. Recent Results Cancer Res., 123: 1, 1991.
237. Raghavan, D., Sullivan, A. L., Peckham, M. J. and Neville, A. M.: Elevated serum alphafetoprotein and seminoma: clinical evidence for a histological continuum? Cancer, 50: 982, 1982.
238. Oliver, R. T.: HLA phenotype and clinicopathological behaviour of germ cell tumours: possible evidence for clonal evolution from seminomas and nonseminomas. Int. J. Androl., 10: 85, 1987.
239. Damjanov, I.: Pathogenesis of testicular germ cell tumours. Eur. Urol., 23: 2, 1993.
240. Pitot, H. C.: Characterization of the stages of progression in hepatocarcinogenesis in the rat. In: Boundaries Between Promotion and Progression During Carcinogenesis. Edited by O. Sudilovsky, H. C. Pitot and L. A. Liotta. New York: Plenum Press, vol. 57, pp. 3-18, 1991.
241. Oliver, R. T.: Atrophy, hormones, genes and viruses in aetiology of germ cell tumours. Cancer Surv., 9: 263, 1990.
242. Heimdal, K, Fosså, S. D., Brøgger, A. and Møller, P.: No evidence for constitutional chromosome instability in testicular cancer. Hum. Genet., 89: 338, 1992.
243. Lothe, R. A., Heimdal, K., Lier, M. E., Fosså, S. D., Møller, P. and Brøgger, A.: High resolution chromosome banding in search for germ line mutations applied on testicular cancer patients. Cancer Genet. Cytogenet., 59: 62, 1992.
244. Wang, N., Perkins, K. L., Bronson, D. L. and Fraley, E. E.: Cytogenetic evidence for premeiotic transformation of human testicular cancers. Cancer Res., 41: 2135, 1981.
245. Müller, J. and Skakkebaek, N. E.: Microspectrophotometric DNA measurements of carcinoma-in-situ germ cells in the testis. Int. J. Androl., suppl., 4: 211, 1981.
246. Müller, J.: Abnormal infantile germ cells and development of carcinoma-in-situ in maldeveloped testes. A stereological and densitometric study. Int. J. Androl., 10: 543, 1987.
247. Vorechovsky, I. and Mazanec, K.: Cytogenetic investigation of gonadal carcinomas in situ in syndromes of abnormal differentiation. Pathobiology of human germ cell neoplasia. Recent Results Cancer Res., 123: 45, 1991.
248. Giwercman, A., Müller, J. and Skakkebaek, N. E.: Prevalence of carcinoma in situ and other histopathological abnormalities in testes from 399 men who died suddenly and unexpectedly. J. Urol., 145: 77, 1991.
249. Harris, H.: The genetic analysis of malignancy. J. Cell, suppl., 4: 431, 1986.
250. Sager, R.: Genetic suppression of tumor formation: a new frontier in cancer research. Cancer Res., 46: 1573, 1986.
251. Swerdlow, A. J.: The epidemiology of testicular cancer. Eur Urol., suppl. 2, 23: 35, 1993.
252. Forman, D., Oliver, R. T., Brett, A. R., Marsh, S. G., Moses, J. H., Bodmer, J. G., Chilvers, C. E. and Pike, M. C.: Familial testicular cancer: a report of the UK family register, estimation of risk and an HLA class 1 sib-pair analysis. Brit. J. Cancer, 65: 255, 1992.
253. Dieckmann, K. P., Klän, R. and Bünte, S.: HLA antigens, Lewis antigens, and blood groups in patients with testicular germ-cell tumors. Oncology, 50: 252, 1993.
254. Murty, V. V., Bosl, G. J., Houldsworth, J., Meyers, M., Mukherjee, A. B., Reuter, V. E. and Chaganti, R. S.: Allelic loss and somatic differentiation in human male germ cell tumors. Oncogene, 9: 2245, 1994.