Zusammenfassung
Wir wissen heute, daß Krebs eine genetische Erkrankung ist. Ausgangspunkt in der Entstehung eines jeden Tumors ist eine irreversible Änderung, d. h. eine Mutation irgendwo im Erbgut (Genom). Die betroffene Zelle im Organismus ist „initiiert“, sie kann sich, durch Tumorpromotoren stimuliert, einen Wachstumsvorsprung gegenüber den Nachbarzellen verschaffen. Sie ist aber noch nicht in der Lage, zu einem Tumor auszuwachsen. Zur Entstehung eines gutartigen Tumors und hieraus zu einem soliden Tumor kann jeweils eine weitere genetische Änderung (Mutation) notwendig sein. Da Tumorzellen genetisch zunehmend instabil werden, ist auch die Wahrscheinlichkeit der Ausprägung von Tumorzellheterogenitäten und der Tumorprogression unter Bildung von metastasierenden Subklonen in erhöhtem Maße gegeben. Dieser, in Abb. 1 schematisch dargestellte, mehrstufige Ablauf der Karzinogenese dürfte für die meisten soliden Tumoren (mit Ausnahme des Retinoblastoms, s. unten) zutreffen. Welche Gene sind betroffen und welcher Natur sind die genetischen Änderungen?
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Literatur
Baker SJ, Markowitz S, Fearon ER, Willson JKV, Vogelstein B (1990) Science 249:912–915
Bremner R, Balmain A (1990) Genetic changes in skin tumor progression: Correlation between presence of a mutant ras gene and loss of heterozygosity on mouse chromosome 7. Cell 61:407–417
Bosch FX, Schwarz E, Boukamp P, Bartsch D, zur Hausen H (1990) Suppression in vivo of human papillomavirus type 18 E6-E7 gene expression in nontumorigenic HeLa X fibroblast hybrid cells. J Virol 64:4734–4754
Buetow KH, Murray JC, Israel JL et al. (1989) Loss of heterozygosity suggests tumor suppressor gene responsible for primary hepatocellular carcinoma. Proc Natl Acad Sci USA 86:8852–8856
Call KM, Glaser T, Ito CY et al. (1990) Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms’ tumor locus. Cell 60:509–520
DeCaprio JA, Ludlow JW, Figge J et al. (1988) Sv40 large tumor antigen forms a specific complex with the product of the retinoblastoma susceptibility gene. Cell 54:275–283
Durst M, Bosch FX, Glitz D, Schneider A, zur Hausen H (1991) Inverse relationship between HPV 16 early gene expression and cell differentiation in nude mouse epithelial cysts and tumors induced by HPV positive human cell lines J Virol 65:796–804
Fearon ER, Cho KR, Nidro JM (1990) Identification of a chromosome 18q gene that is altered in colorectal cancers. Science 247:49–56
Fearon ER, Vogelstein B (1990) A genetic model for colorectal tumorigenesis. Review. Cell 61:759–767
Geiser AG, Der CJ, Mashall CJ, Stanbridge EJ (1986) Suppression of tumorigenicity with continued expression of the c-Ha-ras oncogene in EJ bladder carcinoma-human fibroblast hybrid cells. Proc Natl Acad Sci USA 83:5209–5213
Hansen MF, Cavanee WK (1987) Genetics of cancer predisposition. Cancer Res 47:5518–5527
Harris H, Miller OJ, Klein G, Worst P, Tachibana T (1969) Suppression of malignancy by cell fusion. Nature 223:363–368
Knudson AG (1971) Matation and cancer: Statistical study of retinoblastoma. Proc Natl Acad Sci USA 68:820–823
Knudson AG (1985) Hereditary cancer, oncogenes and antioncogenes. Cancer Res 45:1437–1443
Knudson AG (1989) Hereditary cancers: clues to mechanisms of carcinogeneis. The Ninth Gordon Hamilton-Fairley Memorial Lecture. Br J Cancer 59:661–666
Levine AJ (1990) Minireview: The p53 protein and its interactions with the oncogene products of the small DNA tumor viruses. Virology 177:419–426
Ludlow JW, DeCaprio JA, Huang C-M, Lee W-H, Paucha E, Livingston DM (1989) SV40 large T antigen binds preferentially to an underphosphorylated member of the retinoblastoma susceptability gene product family. Cell 56:57–65
Matlashewski G, Schneider J, Banks L, Jones N, Murray A, Crawford L (1987) Human papillomavirus type 16 DNA cooperates with activated RAS in transforming primary cells. EMBO J 6:1741–1746
Mercer WE, Shields MT, Amin M, Sauve GJ, Appella E, Romano JW, Ullrich SJ (1990) Negative growth regulation in a glioblastoma tumor cell line that conditionally expresses human wildtype p53. Proc Natl Acad Sci USA 87:6166–6170
Michalovitz D, Halevy O, Oren M (1990) Conditional inhibition of transformation and of cell proliferation by a temperature-sensitive mutant of p53. Cell 62:671–680
Milner J, Cook A, Mason J (1990) p53 is associated with p34cdc2 in transformed cells. EMBO J 9:2885–2889
Münger K, Phelps WC, Bubb V, Howley PM, Schlegel R (1989) The E6 and E7 genes of the human papillomavirus type 16 together are necessary and sufficient for transformation of primary human keratinocytes. J Virol 63:4417–4421
Ray croft L, Wu H, Lozano G (1990) Transcriptional activation by wild-type but not transforming mutants of the p53 antioncogene. Science 249:1049–1051
Sager R (1989) Tumor suppressor genes: The buzzle and the promise. Science 246:1406–1412
Spandidos DA, Anderson MLM (1989) Review article: Oncogenes and oncosuppressor genes: Their involvement in cancer. J Pathol 157:1–10
Stanbridge EJ (1976) Suppression of malignancy in human cells. Nature 260:17–20
Stanbridge EJ, Flandermayer RR, Daniels DW, Nelson-Rees WA (1981) Specific chromosome loss associated with the expression of tumorigenicity in human cell hybrids. Somatic Cell Mol Genet 7:699–712
Stanbridge EJ, Der CJ, Doersen CJ, Nishimi RY, Peehl DM, Weissma BE, Wilkinson JE (1982) Human cell hybrids: Analysis of transformation and tumorigenicity. Science 215:252–259
Stanbridge EJ (1989) A genetic basis for tumor suppression. In: Genetic analysis of tumour suppression. Wiley, Chichester (Ciba Foundation Symposium 142) pp 149–165
Stanbridge EJ (1990) Identifying tumor suppressor genes in human colorectal cancer. Science 247:12–13
Suzuki T, Yokota J, Mugishima H, Okabe I, Ookuni M, Sugimura T, Terada M (1989) Frequent loss of heterogeneity on chromosome 14q in neuroblastoma. Cancer Res 49:1095–1098
Trent JM, Meyskens FL, Salmon SE, Ryschon K, Leong SPL, Davis JR, McGee DL (1990) Relation of cytogenetic abnormalities and clinical outcome in metastatic melanoma. N Engl J Med 322:1508–1511
Tsuda H, Zhang W, Shimosato Y et al. (1990) Allele loss on chromosome 16 associated with progression of human hepatocellular carcinoma. Proc Natl Acad Sci USA 87:6791–6794
Weinberg RA (1990) The retinoblastoma gene and cell growth control. TIBS 15:199–202
Weinberg RA (1989) Oncogenes, antioncogenes, and the molecular bases of multistep carcinogenesis. Perspectives in cancer research. Cancer Res 49:3713–3721
Weissmann BE, Saxon PJ, Pasquale SR, Jones GR, Geiser AG, Stanbridge EJ (1987) Introduction of a normal chromosome 11 into a Wilms’ tumor cell line controls its tumorigenic expression. Science 236:175–180
Zur Hausen H (1986) Intracellular surveillance of persisting viral infections. Lancet 11:489–491
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1991 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Bosch, F.X. (1991). Was wissen wir heute über die Bedeutung genetischer Faktoren für die Entstehung maligner Tumoren?. In: Maier, H., Weidauer, H. (eds) Krebsrisiken im Kopf-Hals-Bereich. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-76036-5_21
Download citation
DOI: https://doi.org/10.1007/978-3-642-76036-5_21
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-53084-8
Online ISBN: 978-3-642-76036-5
eBook Packages: Springer Book Archive