Zusammenfassung
Das Spektrum der gynäkologischen Tumoren reicht von funktionellen Veränderungen über tumorartige Proliferate bis hin zu echten Neoplasien und zeichnet sich durch eine hohe klinische Variabilität aus. Eine zuverlässige Einschätzung dieser Läsionen ist für das therapeutische Vorgehen von hoher Bedeutung.
Tumorentstehung wird heute als mehrstufiger Prozess begriffen, der mit der unkontrollierten Proliferation von Zellen beginnt und über klonale Selektion, Immortalisierung und Akkumulation chromosomaler Aberrationen zur Entwicklung eines invasiven und metastasierenden Tumors führt.
In den vergangenen Jahren konnten durch Fortschritte im Bereich der Molekularbiologie detaillierte Einblicke in die molekulare Pathogenese gewonnen werden. Dadurch wurden einige neue diagnose- und therapierelevante Biomarker (z. B. Her2/neu, upa/pai I) identifiziert, die bereits heute eine individualisierte risikoadaptierte Therapie für einzelne Tumorentitäten ermöglichen.
Abstract
Human female genital tumors comprise heterogeneous lesions including benign, precancerous proliferations and malignant tumors with a high clinical variability. An in-depth understanding of the pathogenesis of these lesions is important for accurate diagnosis and management. To date tumors are viewed as a result of a multistep process with various abnormalities that contribute to tumor development.
Tumorigenesis proceeds through a series of molecular alterations involving uncontrolled cell proliferation, clonal expansion, immortalization, and accumulation of chromosomal aberrations. Major advances in molecular biology provide a better understanding of the molecular pathogenesis of malignant tumors.
The identification of new diagnostically and therapeutically relevant biomarkers (e.g., Her2/neu, upa/pai I) already allows individualized management of some tumor entities.
Literatur
Albertson DG, Collins C, McCormick F, Gray JW (2003) Chromosome aberrations in solid tumors. Nat Genet 34: 369–376
Blasco MA (2002) Telomerase beyond telomeres. Nat Rev Cancer 2: 627–633
Bodnar AG, Ouellette M, Frolkis M et al. (1998) Extension of life-span by introduction of telomerase into normal human cells. Science 279: 349–352
Boveri T (1914) Zur Frage der Enstehung maligner Tumoren. Fischer, Jena
Fan X, Wang Y, Kratz J et al. (2003) hTERT gene amplification and increased mRNA expression in central nervous saystem embryonal tumors. Am J Pathol 162: 1763–1769
Fearon ER, Vogelstein B (1990) A genetic model for colorectal tumorigenesis. Cell 61: 759–767
Fishel R, Lescoe MK, Rao MR et al. (1993) The human mutator gene homolog MSH 2 and ist association with hereditary nonpolyposis colon cancer. Cell 75: 1027–1038
Fisk HA, Mattison CP, Winey M (2002) Centrosomes and tumour suppressors. Curr Opin Cell Biol 14: 700–705
Friend SH, Bernards R, Rogelj S, Weinberg RA, Rapport JM Albers DM, Dryja TP (1986) A human DANN segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature 323: 643–646
Goldberg DM, Diamandis EP (1993) Models of neoplasia and their diagnostic implications: a historical perspective. Clin Chem 39: 2360–2374
Hartwell L, Weinert T, Kadyk L, Garvik B (1994) Cell cycle checkpoints, genomic integrity, and cancer. Cold Spring Harb Symp Quant Biol 59: 259–263
Henson JD, Neumann AA, Yeager TR, Reddel R (2002) Alternative lengthening of telomeres in mammalian cells. Oncogene 21: 598–610
Hernadi Z, Szarka K, Sapy T, Krasznai Z, Veress G, Poka R (2003) The prognostic significance of HPV-16 genome status of the lymph nodes, the integration status and p53 genotype in HPV-16 positive cervical cancer: a long term follow up. BJOG 110: 205–209
Hsu SH, Luk GD, Krush AJ, Hamilton SR, Hoover HH Jr (1983) Multiclonal origin of polyps in Gardner syndrome. Science 221: 951–953
Jallepalli PV, Lengauer C (2001) Chromsome segregation and cancer:cutting through the mystery. Nat Rev Cancer 1: 109–117
Kiyono T, Foster SA, Koop JL, McDougall JK, Galloway DA, Klingelhutz AJ (1998) Both Rb/p16INK4a inactivation and telomerase activity are required to immortalize human epithelial cells. Nature 396: 84–88
Lawley PD (1994) Historical origins of current concepts of carcinogenis. Adv Cancer Res 65: 17–111
Lengauer C, Kinzler KW, Vogelstein B (1998) Genetic instabilities in human cancers. Nature 396: 643–649
Lynch HT, de la Chapelle A (2003) Hereditary colorectal cancer. N Engl J Med 348: 919–932
Lyon MF (1999) Imprinting and X-chromosome inactivation. Results Probl Cell Differ 25: 73–90
Malkin D, Li FP, Strong LC et al.(1990) Germ line p53 mutations in familial syndrome of breast cancer, sarcomas, and other neoplasms. Science 250: 1233–1238
Miller EC, Miller JA (1974) The molecular biology of cancer. Academic Press, New York
Nakamura Y (1998) ATM: p53 booster. Nat Med 4: 1231–1232
Park TW, Richart RM, Sun XW, Wright TC Jr (1996) Association between human papillomavirus type and clonal status of cervical squamous intraepithelial lesions. J Natl Cancer Inst 88: 355–358
Park TW, Felix JC, Wright TC Jr (1995) X chromosome inactivation and microsatellite instability in early and advanced bilateral ovarian carcinomas. Cancer Res 55: 4793–4796
Potter V (1957) The present status of the deletion hypothesis. Univ Mich Med Bull 23: 400–412
Steen HB (2000) The origin of oncogneic mutations: where is the damage. Carcinogenesis 21: 1773–1776
Temin HM (1965) The mechanism of carcinogenesis by avian sarcoma viruses. 1. Cell multiplication and differentiation. J Natl Cancer Inst 35: 679–693
Varmus HE (1984) The molecular genetics of cellular oncogenes. Ann Rev Genet 18: 553–612
Vulliamy T, Marrone A, Goldman F, Dearlove A, Bessler M, Mason PJ, Dokal I (2001) The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenita. Nature 413: 432–435
Vulliamy T, Marrone A, Dokal I, Mason PJ (2002) Association between aplastic anaemia and mutations in telomerase RNA. Lancet 359: 2168–2170
Zhang A, Zheng C, Hou M et al. (2002) Amplification of the telomerase reverse transcriptase (hTERT) gene in cervical carcinomas. Genes Chromosomes Cancer 34: 269–275
Interessenkonflikt:
Der korrespondierende Autor versichert, dass keine Verbindungen mit einer Firma, deren Produkt in dem Artikel genannt ist, oder einer Firma, die ein Konkurrenzprodukt vertreibt, bestehen.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Park, T.W., Simon, M. Molekulare Grundmechanismen in der Onkogenese. Gynäkologe 37, 196–202 (2004). https://doi.org/10.1007/s00129-004-1494-y
Issue Date:
DOI: https://doi.org/10.1007/s00129-004-1494-y