Abstract
Ovarian cancer is one of the most severe of oncological diseases. Inherited mutations in cancer susceptibility genes play a causal role in 5–10% of newly diagnosed tumours.BRCA1 andBRCA2 gene alterations are found in the majority of these cases. The aim of this study was to analyse theBRCA1 gene in the ovarian cancer risk group to characterize the spectrum of its mutations in the Czech Republic. Five overlapping fragments amplified on both genomic DNA and cDNA were used to screen for the whole proteincoding sequence of theBRCA1 gene. These fragments were analysed by the protein truncation test (PTT) and direct sequencing. Three inactivating mutations were identified in the group of 30 Czech ovarian cancer patients: the 5382insC mutation in two unrelated patients and a deletion of exons 21 and 22 in another patient. In addition, we have found an alternatively spliced product lacking exon 5 in two other unrelated patients. The 5382insC is the most frequent alteration of theBRCA1 gene in Central and Eastern Europe. The deletion of exons 21 and 22 affects the BRCT functional domain of the BRCA1 protein. Although large genomic rearragements are known to be relatively frequent in Western European populations, no analyses have been performed in our region yet.
Similar content being viewed by others
References
Apicella C., Andrews L., Hodgson S. V., Fisher S. A., Lewis C. M., Solomon E.et al. 2003 Log odds of carrying an ancestral mutation in BRCA1 or BRCA2 for a defined personal and family history in an Ashkenazi Jewish woman (LAMBDA).Breast Cancer Res. 5, R206–216.
Bartonkova H., Foretova L., Helmichova E., Kalabova R., Kleibl Z., Konopasek B.et al. 2003 Doporučené zásady péče o nemocné s nádory prsu a vaječníků a zdravé osoby se zárodečnými mutacemi genů BRCA1 nebo BRCA2.Klin. Onkol. 16, 28–34.
Beaudet A. L.and Tsui L.-C. 1993 A suggested nomenclature for designating mutations.Hum. Mutat. 2, 245–248.
Eeles R. and Kadouri L. 1999BRCA1/2 carriers and endocrine risk modifiers.Endocrine-Related Cancer 6, 521–528.
Ford D., Easton D. F., Bishop D. T., Narod S. A. and Goldgar D. E. 1994 Risks of cancer inBRCA1 -mutation carriers.Lancet 343, 692–695.
Foretova L., Machackova E., Navratilova M., Pavlu H., Hruba M., Lukesova M. and Valik D. 2004BRCA1 andBRCA2 mutations in women with familial or earlyonset breast/ovarian cancer in the Czech Republic.Hum. Mutat. 23, 397–398.
Grzybowska E., Sieminska M., Zientek H., Kalinowska E., Michalska J., Utracka-Hutka B.et al. 2002 Germline mutations in theBRCA1 gene predisposing to breast and ovarian cancers in Upper Silesia population.Acta Biochim. Pol. 49, 351–356.
Hall J. M., Lee M. K., Newman B., Morrow J. E., Anderson L. A., Huey B.et al. 1990 Linkage of earlyonset familial breast cancer to chromosome 17q21.Science 250, 1684–1689.
Hogervorst F. B. L., Cornelis R. S., Bout M., vanVliet M., Oosterwijk J. C., Olmer R.et al. 1995 Rapid detection ofBRCA1 mutations by the protein truncation test.Nat. Genet. 10, 208–212.
Janatova M., Pohlreich P. and Matous B. 2003 Detection of the most frequent mutations inBRCA1 gene on polyacrylamide gels containing Spreadex Polymer NAB.Neoplasma 50, 246–250.
Jancarkova N., Zikan M., Pohlreich P., Freitag P., Matous B. and Zivny J. 2003 Detection and occurrence ofBRCA1 gene mutation in patients with carcinoma of the breast and ovary.Cas. Lek. Cesk. 68, 11–16.
Machackova E., Foretova L., Navratilova M., Valik D., Claes K. and Messiaen L. 2000 A high occurrence of BRCA1 and BRCA2 mutations among Czech hereditary breast and breastovarian cancer families.Cas. Lek. Cesk. 139, 635–637.
Machackova E., Damborsky J., Valik D. and Foretova L. 2001 Novel germline BRCA1 and BRCA2 mutations in breast and breast/ovarian cancer families from the Czech Republic.Hum. Mutat. 18, 545.
Maquat L. E. 1995 When cells stop making sense: effects of nonsense codons on RNA metabolism in vertebrate cells.RNA 1, 453–465.
Miki Y., Swensen J., Shattuck-Eidens D., Futreal P. A., Harshman K., Tavtigian S.et al. 1994 A strong candidate for the breast and ovarian cancer susceptibility gene,BRCA1.Science 266, 66–71.
Monteiro A. N. A. 2000 BRCA1: exploring the links to transcription.Trends Biochem. Sci. 25, 469–474.
Offit K., Gilewski T., McGuire P., Schluger A., Hampel H., Brown K.et al. 1996 GermlineBRCA1 185delAG mutation in Jewish women with breast cancer.Lancet 347, 1643–1645.
Perkowska M., Brozek I., Wysocka B., Haraldsson K., Sandberg T., Johansson U., Sellberg G.et al. 2003BRCA1 andBRCA2 mutation analysis in breastovarian cancer families from northeastern Poland.Hum. Mutat. 21, 553–554.
Petrij-Bosch A., Peelen T., van Vliet M., van Eijk R., Olmer R., Drüsedau M.et al. 1997 BRCA1 genomic deletions are major founder mutations in Dutch breast cancer patients.Nat. Genet. 17, 341–345.
Pohlreich P., Stribrna J., Kleibl Z., Zikan M., Kalbacova R., Petruzelka L. and Konopasek B. 2003 Mutations of theBRCA1 gene in hereditary breast and ovarian cancer in the Czech Republic.Med Princ Pract. 12, 23–29.
Puget N., Gad S. and Perrin-Vidoz L. 2002 Distinct BRCA1 rearrangements involving theBRCA1 pseudogene suggest the existence of a recombination hot spot.Am. J. Hum. Genet. 70, 858–865.
Rohlfs E. M., Chung C. H., Yang Q., Skrzynia C., Grody W. W., Graham M. L. and Silverman L. M. 2000 Inframe deletions of BRCA1 may define critical functional domains.Hum. Genet. 107, 385–390.
Scully R., Anderson S. F., Chao D. M., Wei W., Ye L., Young R. A.et al. 1997BRCA1 is a component of the RNA polymerase II holoenzyme.Proc. Natl. Acad. Sci. USA 94, 5605–5610.
Serova O., Montagna M., Torchard D., Narod S. A., Tonin P. and Sylla B. 1996 A high incidence ofBRCA1 mutations in 20 breastovarian cancer families.Am. J. Hum. Genet. 58, 42–51.
Shattuck-Eidens D., Oliphant A., McClure M., McBride C., Gupte J., Rubano T.et al. 1997BRCA1 sequence analysis in women at high risk for susceptibility mutations.J. Am. Med. Assoc. 278, 1242–1250.
Starita L. M. and Parvin J. D. 2003 The multiple nuclear functions ofBRCA1: transcription, ubiquitination and DNA repair.Curr. Opin. Cell Biol. 15, 345–350.
Welcsh P. L. and King M. 2001BRCA1 andBRCA2 and the genetics of breast and ovarian cancer.Hum. Mol. Genet. 10, 705–713.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Zikan, M., Pohlreich, P. & Stribrna, J. Mutational analysis of theBRCA1 gene in 30 Czech ovarian cancer patients. J Genet 84, 63–67 (2005). https://doi.org/10.1007/BF02715891
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02715891