Abstract
This chapter is an overview, from a technical perspective, of the approaches that can be used to analyze genetic changes in ovarian cancers. Traditional gene localization methods are discussed, followed by a section on gene identification techniques. Once a putative disease-associated gene has been cloned, mutations have to be identified and analyzed. There are numerous mutation detection methods, and the most common ones are outlined. In the penultimate section, the role of immunohistochemistry as a surrogate method for mutation analysis is considered. Finally, the possible use of functional assays is discussed. The number of techniques used in the molecular analysis of ovarian cancer is immense, and it is beyond the scope of this book to describe all of these methods. However, the most important methods have been outlined in this overview chapter, and many are described in detail in the following chapters.
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References
Friend, S. H., Bernards, R., Rogelj, S., et al. (1986) A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature 323, 643–646.
Miki, Y., Swensen, J., Shattuck-Eidens, D., et al. (1994) A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 266, 66–71.
Wooster, R., Bignell, G., Lancaster, J., et al. (1995) Identification of the breast cancer susceptibility gene BRCA2. Nature 378, 789–792.
Miki, Y., Katagiri, T., Kasumi, F., Yoshimoto, T., and Nakamura, Y. (1996) Mutation analysis in the BRCA2 gene in primary breast cancers. Nature Genet. 13, 245–247.
Futreal, P. A., Liu, Q., Shattuck-Eidens, D., et al. (1994) BRCA1 mutations in primary breast and ovarian carcinomas. Science 266, 120–122.
Merajver, S. D., Pham, T. M., Caduff, R. F., et al. (1995) Somatic mutations in the BRCA1 gene in sporadic ovarian tumors. Nature Genet. 9, 439–443.
Foster, K. A., Harrington, P., Kerr, J., et al. (1996) Somatic and germline mutations of the BRCA2 gene in sporadic ovarian cancer. Cancer Res. 56, 3622–3625.
Scully, R., Chen, J., Plug, A., et al. (1997) Association of BRCA1 with Rad51 in mitotic and meiotic cells. Cell 88, 265–275.
Kupryjanczyk, J., Thor, A. D., Beauchamp, R., et al. (1993) p53 gene mutations and protein accumulation in human ovarian cancer. Proc. Natl. Acad. Sci. USA 90, 4961–4965.
Fajac, A., Benard, J., Lhomme, C., et al. (1995) c-erbB2 gene amplification and protein expression in ovarian epithelial tumors: evaluation of their respective prognostic significance by multivariate analysis. Int. J. Cancer 64, 146–151.
Pieretti, M., Cavalieri, C., Conway, P. S., Gallion, H. H., Powell, D. E., and Turker, M. S. (1995) Genetic alterations distinguish different types of ovarian tumors. Int. J. Cancer 64, 434–440.
St. Jean, P. and Schork, N. (1988) Genetic epidemiologic approaches to finding genes that influence susceptibility to cancer, in Inherited susceptibility to cancer: clinical, predictive and ethical perspectives, Foulkes, W. D. and Hodgson, S. V., eds. Cambridge: CUP, pp. 109–133.
Narod, S. A., Feunteun, J., Lynch, H. T., et al. (1991) Familial breast-ovarian cancer locus on chromosome 17q12-q23. Lancet 338, 82,83.
Lastowska, M. A., Lillington, D. M., Shelling, et al. (1994) Fluorescence in situ hybridization analysis using cosmid probes to define chromosome 6q abnormalities in ovarian carcinoma cell lines. Cancer Genet Cytogenet. 77, 99–105.
Kallioniemi, A., Kallioniemi, O. P., Sudar, D., et al. (1992) Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors. Science 258, 818–821.
Bentz, M., Plesch, A., Stilgenbauer, S., Dohner, H., and Lichter, P. (1998) Minimal sizes of deletions detected by comparative genomic hybridization. Genes, Chromosomes Cancer 21, 172–175.
Speicher, M. R., Gwyn, Ballard, S., and Ward, D. C. (1996) Karyotyping human chromosomes by combinatorial multi-fluor FISH. Nature Genet. 12, 368–375.
Stanbridge, E. J. (1992) Functional evidence for human tumor suppressor genes: chromosome and molecular genetic studies. Cancer Surveys 12, 5–24.
Rimessi, P., Gualandi, F., Morelli, C., et al. (1994) Transfer of human chromosome 3 to an ovarian carcinoma cell line identifies three regions on 3p involved in ovarian cancer. Oncogene 9, 3467–3474.
Cooke, I. E., Shelling, A. N., Le Meuth, V. G., Charnock, F. M. L., and Ganesan, T. S. (1996) Allele loss on chromosome arm 6q and fine mapping of the region at 6q27 in epithelial ovarian cancer. Genes, Chromosomes, Cancer 14, 223–233.
Bustamante, C., Gurrieri, S., and Smith, S. B. (1993) Towards a molecular description of pulsed-field gel electrophoresis. Trends In Biotechnol. 11, 23–30.
Lisitsyn, N. A., Lisitsina, N. M., Dalbagni, G., et al. (1995) Comparative genomic analysis of tumors: detection of DNA losses and amplification. Proc. Natl. Acad. Sci. USA 92, 151–155.
Schutte, M., da Costa, L. T., Hahn, S. A., et al. (1995) Identification by representational difference analysis of a homozygous deletion in pancreatic carcinoma that lies within the BRCA2 region. Proc. Natl. Acad. Sci. USA 92, 5950–5954.
Hahn, S. A., Schutte, M., Hoque, A. T. M. S., et al. (1996) DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1. Science 271, 350–353.
Howe, J. R., Roth, S., Ringold, J. C., et al. (1998) Mutations in the SMAD4/DPC4 gene in juvenile polyposis. Science 280, 1086–1088.
Liang, P. and Pardee, A. B. (1992) Differential display of eukaryotic messenger RNA by means of the polymerase chain reaction. Science 257, 967–971.
Orita, M., Iwahana, H., Kanazawa, H., Hayashi, K., and Sekiya, T. (1989) Detection of polymorphisms of human DNA by gel electrophoresis as single-strand conformation polymorphisms. Proc. Natl. Acad. Sci. USA 86, 2766–2770.
Stratton, J. F., Gayther, S. A., Russell, P., et al. (1997) Contribution of BRCA1 mutations to ovarian cancer. N. Engl. J. Med. 336, 1125–1130.
Ganguly, A., Rock, M. J., and Prockop, D. J. (1993) Conformation-sensitive gel electrophoresis for rapid detection of single-base differences in double-stranded PCR products and DNA fragents: evidence for solvent-induced bends in DNA heteroduplexes. Proc. Natl. Acad. Sci. USA 90, 10,325–10,329.
Cotton, R. G. and Campbell, R. D. (1989) Chemical reactivity of matched cytosine and thymine bases near mismatched and unmatched bases in a heteroduplex between DNA strands with multiple differences. Nucleic Acids Res. 17, 4223–4233.
FitzGerald, M. G., MacDonald, D. J., Krainer, M., et al. (1996) Germ-line BRCA1 mutations in Jewish and non-Jewish women with early-onset breast cancer. N. Engl. J. Med. 334, 143–149.
Hacia, J. G., Brody, L. C., Chee, M. S., Fodor, S. P., and Collins, F. S. (1996) Detection of heterozy-gous mutations in BRCA1 using high density oligonucleotide arrays and two-colour fluorescence analysis. Nature Genet. 14, 441–447.
King, B. L., Carcangiu, M. L., Carter, D., et al. (1995) Microsatellite instability in ovarian neo plasms. Br. J. Cancer 72, 376–382.
Orth, K., Hung, J., Gazdar, A., Bowcock, A., Mathis, J. M., and Sambrook, J. (1994) Genetic insta bility in human ovarian cancer cell lines. Proc. Natl. Acad. Sci. USA 91, 9495–9499.
Casey, G., Lopez, M. E., Ramos, J. C., et al. (1996) DNA sequence analysis of exons 2 through 11 and immunohistochemical staining are required to detect all known p53 alterations in human malignancies. Oncogene 13, 1971–1981.
Ishioka, C., Frebourg, T., Yan, Y. X., et al. (1993) Screening patients for heterozygous p53 mutations using a functional assay in yeast. Nature Genet. 5, 124–129.
Ishioka, C., Suzuki, T., FitzGerald, M., et al. (1997) Detection of heterozygous truncating mutations in the BRCA1 and APC genes by using a rapid screening assay in yeast. Proc. Natl. Acad. Sci. USA 94, 2449–2453.
Humphrey, J. S., Salim, A., Erdos, M. R., Collins, F. S., Brody, L. C., and Klausner, R. D. (1997) Human BRCA1 inhibits growth in yeast: potential use in diagnostic testing. Proc. Natl. Acad. Sci. USA 94, 5820–5825.
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Foulkes, W., Shelling, A.N. (2000). Molecular Genetics of Ovarian Cancer. In: Bartlett, J.M.S. (eds) Ovarian Cancer. Methods in Molecular Medicine™, vol 39. Humana Press. https://doi.org/10.1385/1-59259-071-3:273
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DOI: https://doi.org/10.1385/1-59259-071-3:273
Publisher Name: Humana Press
Print ISBN: 978-0-89603-583-6
Online ISBN: 978-1-59259-071-1
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