Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Short Report
  • Published:

Identification of a 3 kb Alu-mediated BRCA1 gene rearrangement in two breast/ovarian cancer families

Abstract

Most of the hereditary breast cancers are attributed to constitutive alterations of either BRCA1 or BRCA2 genes; nonetheless, germline mutations of these genes in `high risk' families are found less frequently than expected from linkage data. Recent findings suggest that major genomic rearrangements of the BRCA1 gene might account for at least some of the apparently mutation negative cases. We studied 60 affected probands belonging to families with a strong history of breast and/or ovarian cancer who scored negative for BRCA1 gene mutations by PTT and SSCP analysis. DNA was analysed by the Southern blotting procedure using three different restriction enzymes, and two probes obtained by RT – PCR of the 5′ and 3′ BRCA1 coding sequence. A 3 kb deletion encompassing exon 17 and causing a frameshift mutation was identified in two independently ascertained families. RT – PCR and long-range DNA PCR were employed to characterize the rearrangement that was finally shown to be the result of a recombination between two very similar Alu repeats. This type of mutation is not identified by the conventional methods of mutation detection which are based on PCR amplification of single exons. Therefore, further search for gene rearrangements is needed to better define the proportion of `high risk' families that might be explained by gross genomic alterations of the BRCA1 gene.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  • Claus EB, Risch N and Thompson WD. . 1991 Am. J. Hum. Genet. 48: 232–242.

  • Ford D, Easton DF, Stratton M, Narod S, Goldgar D, Devilee P, Bishop DT, Weber B, Lenoir G, Chang-Claude J, Sobol H, Teare MD, Struewing J, Arason A, Scherneck S, Peto J, Rebbeck TR, Tonin P, Neuhausen S, Barkardottir R, Eyfjord J, Lynch H, Ponder BA, Gayther SA, Birth JM, Lindblom A, Stoppa-Lyonnet D, Bignon Y, Borg A, Hamann U, Haites N, Scott RJ, Maugard CM, Vasen H, Seitz S, Cannon-Albright LA, Schofild A, Zelada-Hedman M, and the Breast Cancer Linkage Consortium. . 1998 Am. J. Hum. Genet. 62: 676–689.

  • Friedman LS, Ostermeyer EA, Szabo CI, Dowd P, Lynch ED, Rowel SE and King M-C. . 1994 Nature Genet. 8: 399–404.

  • Gayther SA, Warren W, Mazoyer S, Russell PA, Harrington PA, Chiano M, Seal S, Hamoudi R, van Rensburg EJ, Dunning AM, Love R, Evans G, Easton D, Clayton D, Stratton MR and Ponder BAJ. . 1995 Nature Genet. 11: 428–433.

  • Hogervorst FBL, Cornelis RS, Bout M, van Vliet M, Oosterwijk JC, Olmer R, Bakker B, Klijn JGM, Vasen HFA, Meijers-Heijboer H, Menko FH, Cornelisse CJ, den Dunnen JT, Devilee P and van Ommen G-JB. . 1995 Nature Genet. 10: 208–212.

  • Jacobson A and Pelts SW. . 1996 Annu. Rev. Biochem. 65: 693–739.

  • Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, Liu Q, Cochran C, Bennett LM, Ding W, Bell R, Rosenthal J, Hussey C, Tran T, McClure M, Frye C, Hattier T, Phelps R, Haugen-Strano A, Katcher H, Yakumo K, Gholami Z, Shaffer D, Stone S, Bayer S, Wray C, Bodgen R, Dayananth P, Ward J, Tonin P, Narod S, Bristow PK, Norris FH, Helvering L, Morrison P, Rosteck P, Lai M, Barrett JC, Lewis C, Neuhausen S, Cannon-Albright L, Goldgar D, Wiseman R, Kamb A and Skolnick MH. . 1994 Science 266: 66–71.

  • Montagna M, Santacatterina M, Corneo B, Menin C, Serova O, Lenoir GM, Chieco-Bianchi L and D'Andrea E. . 1996 Cancer Res. 56: 5466–5469.

  • Neuhausen SL, Mazoyer S, Friedman L, Stratton M, Offit K, Caligo A, Tomlinson G, Cannon-Albright L, Bishop T, Kelsell D, Solomon E, Weber B, Couch F, Struewing J, Tonin P, Durocher F, Narod S, Skolnick MH, Lenoir G, Serova O, Ponder B, Stoppa-Lyonnet D, Easton D, King MC and Goldgar DE. . 1996 Am. J. Hum. Genet. 58: 271–280.

  • Petrij-Bosch A, Peelen T, van Vliet M, van Eijk R, Olmer R, Drusedau M, Hogervorst FB, Hageman S, Arts PJ, Ligtenberg MJ, Meijers-Heijboer H, Klijn JG, Vasen HF, Cornelisse CJ, van't Veer LJ, Bakker E, van Ommen GJ and Devilee P. . 1997 Nat. Genet. 17: 341–345.

  • Puget N, Torchard D, Serova-Sinilnikova OM, Lynch HT, Feuteun J, Lenoir GM and Mazoyer S. . 1997 Cancer Res. 57: 828–831.

  • Serova O, Montagna M, Torchard D, Narod SA, Tonin P, Sylla B, Lynch HT, Feunteun J and Lenoir GM. . 1996 Am. J. Hum. Genet. 58: 42–51.

  • Smith TM, Lee MK, Szabo CI, Jerome N, McEuen M, Taylor M, Hood L and King MC. . 1996 Genomic Res. 6: 1029–1049.

  • Swensen J, Hoffman M, Skolnick MH and Neuhausen SL. . 1997 Hum. Mol. Genet. 6: 1513–1517.

  • Szabo CI and King MC. . 1997 Am. J. Hum. Genet. 60: 1013–1020.

  • The Breast Cancer Information Core on the internet (http://www.nchgr.nih.gov/Intramural_research/Lab_transfer/Bic/)

  • Xu CF, Chambers JA, Nicolai H, Brown MA, Hujeirat Y, Mohammed S, Hodgson S, Kelsell DP, Spurr NK, Bishop DT and Solomon E. . 1997 Genes Chromosomes Cancer 18: 102–110.

Download references

Acknowledgements

We thank the family members and the physicians (S Aversa, A Bononi, C Di Maggio, E Ferrazzi, A Fornasiero, V Fosser, O Nascimben, O Nicoletto, A Rosa-Bian, G Zavagno) who contributed to this study; M Quaggio for her expert technical assistance; P Gallo for artwork and P Segato for help in preparing the manuscript. M Montagna and M Santacatterina are fellows of the Associazione and Fondazione Italiana per la Ricerca sul Cancro (AIRC/FIRC), respectively. This study was supported by grants from Ministero della Ricerca Scientifica e Tecnologica (MURST), Italian Hereditary Breast/Ovarian Cancer Consortium/AIRC-Coordinated Project, Regione Veneto/Ricerca Sanitaria Finalizzata, and Fondazione Cassa di Risparmio di Padova e Rovigo, Italy.

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Montagna, M., Santacatterina, M., Torri, A. et al. Identification of a 3 kb Alu-mediated BRCA1 gene rearrangement in two breast/ovarian cancer families. Oncogene 18, 4160–4165 (1999). https://doi.org/10.1038/sj.onc.1202754

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1202754

Keywords

This article is cited by

Search

Quick links