This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Puget, N. Articles by Mazoyer, S. Search for Related Content PubMed PubMed Citation Articles by Puget, N. Articles by Mazoyer, S.

A 1-kb Alu-mediated Germ-Line Deletion Removing BRCA1 Exon 17¹

IARC, 150 Cours Albert Thomas, 69372 Lyon Cedex 08, France [N. P., O. M. S-S., G. M. L., S. M.]; Laboratoire de Génétique, Unité Mixte de Recherche 5641 Centre National de la Recherche Scientifique, Université Claude Bernard, 69373 Lyon Cedex 08, France [N. P., O. M. S-S., G. M. L., S. M.]; Laboratoire de Génétique Oncologique, Unité de Recherche Associée 1964 Centre National de la Recherche Scientifique, Institut Gustave Roussy, 94805 Villejuif, France [D. T., J. F.]; and Department of Preventive Medicine and Public Health, Creighton University School of Medicine, Omaha, Nebraska 68178 [H. T. L.]

Although more than 100 different BRCA1 germ-line mutations have already been identified in breast and/or ovarian cancer families, we report for the first time a deleterious genomic rearrangement in BRCA1. A 1-kb deletion comprising exon 17 was found in a large breast and ovarian cancer family, leading to a frameshift in the mutant mRNA due to the absence of exon 17. This deletion is probably the result of a recombination between two closely related Alu sequences. It was not detected by conventional PCR-based methods involving the genomic screening of the 22 coding exons or reverse transcription-PCR because the transcript without exon 17 is unstable in lymphoblastoid cell lines. Therefore, rearrangements in the BRCA1 gene should be sought in breast/ovarian cancer families in which no mutations have been found by PCR-based methods in the coding region or in the splice sites.

¹ Supported by program grants from le Comité Départemental de l'Ain de La Ligue Nationale contre le Cancer, the Council for Tobacco Research (Grant 127DR@), the Department of the United States Army (Grant DAMD17-94-J-4340), and the Nebraska State Cancer and Smoking-related Diseases Program. N. P. is a fellow of the Ligue contre le Cancer de Haute-Savoie, and S. M. is a recipient of an IARC special training award.

² To whom requests for reprints should be addressed. Phone: 33-4-72-73-85-57; Fax: 33-4-72-73-85-75; E-mail: lenoir@iarc.fr.

Received 11/ 5/96. Accepted 1/17/97.

This article has been cited by other articles:

				F Chibon, C Primois, J-M Bressieux, D Lacombe, C Lok, L Mauriac, A Taieb, and M Longy Contribution of PTEN large rearrangements in Cowden disease: a multiplex amplifiable probe hybridisation (MAPH) screening approach J. Med. Genet., October 1, 2008; 45(10): 657 - 665. [Abstract] [Full Text] [PDF]

				M. D. Palma, S. M. Domchek, J. Stopfer, J. Erlichman, J. D. Siegfried, J. Tigges-Cardwell, B. A. Mason, T. R. Rebbeck, and K. L. Nathanson The Relative Contribution of Point Mutations and Genomic Rearrangements in BRCA1 and BRCA2 in High-Risk Breast Cancer Families Cancer Res., September 1, 2008; 68(17): 7006 - 7014. [Abstract] [Full Text] [PDF]

				M. Soegaard, S. K. Kjaer, M. Cox, E. Wozniak, E. Hogdall, C. Hogdall, J. Blaakaer, I. J. Jacobs, S. A. Gayther, and S. J. Ramus BRCA1 and BRCA2 Mutation Prevalence and Clinical Characteristics of a Population-Based Series of Ovarian Cancer Cases from Denmark Clin. Cancer Res., June 15, 2008; 14(12): 3761 - 3767. [Abstract] [Full Text] [PDF]

				R. Nanda, L. P. Schumm, S. Cummings, J. D. Fackenthal, L. Sveen, F. Ademuyiwa, M. Cobleigh, L. Esserman, N. M. Lindor, S. L. Neuhausen, et al. Genetic Testing in an Ethnically Diverse Cohort of High-Risk Women: A Comparative Analysis of BRCA1 and BRCA2 Mutations in American Families of European and African Ancestry JAMA, October 19, 2005; 294(15): 1925 - 1933. [Abstract] [Full Text] [PDF]

				A M Woodward, T A Davis, A G S Silva, kConFab Investigators, J A Kirk, and J A Leary Large genomic rearrangements of both BRCA2 and BRCA1 are a feature of the inherited breast/ovarian cancer phenotype in selected families J. Med. Genet., May 1, 2005; 42(5): e31 - e31. [Abstract] [Full Text] [PDF]

				J D Fackenthal, L Sveen, Q Gao, E K Kohlmeir, C Adebamowo, T O Ogundiran, A A Adenipekun, R Oyesegun, O Campbell, C Rotimi, et al. Complete allelic analysis of BRCA1 and BRCA2 variants in young Nigerian breast cancer patients J. Med. Genet., March 1, 2005; 42(3): 276 - 281. [Full Text] [PDF]

				O. M. Sinilnikova, S. M. Ginolhac, C. Magnard, M. Leone, O. Anczukow, D. Hughes, K. Moreau, D. Thompson, C. Coutanson, J. Hall, et al. Acetyl-CoA carboxylase {alpha} gene and breast cancer susceptibility Carcinogenesis, December 1, 2004; 25(12): 2417 - 2424. [Abstract] [Full Text] [PDF]

				A. Pavlicek, V. N. Noskov, N. Kouprina, J. C. Barrett, J. Jurka, and V. Larionov Evolution of the tumor suppressor BRCA1 locus in primates: implications for cancer predisposition Hum. Mol. Genet., November 15, 2004; 13(22): 2737 - 2751. [Abstract] [Full Text] [PDF]

				M. Montagna, M. D. Palma, C. Menin, S. Agata, A. De Nicolo, L. Chieco-Bianchi, and E. D'Andrea Genomic rearrangements account for more than one-third of the BRCA1 mutations in northern Italian breast/ovarian cancer families Hum. Mol. Genet., May 1, 2003; 12(9): 1055 - 1061. [Abstract] [Full Text] [PDF]

				B C Hendrickson, D Pruss, E Lyon, and T Scholl Application of haplotype pair analysis for the identification of hemizygous loci J. Med. Genet., May 1, 2003; 40(5): 346 - 347. [Abstract] [Full Text] [PDF]

				L. Perrin-Vidoz, O. M. Sinilnikova, D. Stoppa-Lyonnet, G. M. Lenoir, and S. Mazoyer The nonsense-mediated mRNA decay pathway triggers degradation of most BRCA1 mRNAs bearing premature termination codons Hum. Mol. Genet., November 1, 2002; 11(23): 2805 - 2814. [Abstract] [Full Text] [PDF]

				J. Goffin and E. Eisenhauer DNA methyltransferase inhibitors--state of the art Ann. Onc., November 1, 2002; 13(11): 1699 - 1716. [Abstract] [Full Text] [PDF]

				S Gad, M Klinger, V Caux-Moncoutier, S Pages-Berhouet, M Gauthier-Villars, I Coupier, A Bensimon, A Aurias, and D Stoppa-Lyonnet Bar code screening on combed DNA for large rearrangements of the BRCA1 and BRCA2 genes in French breast cancer families J. Med. Genet., November 1, 2002; 39(11): 817 - 821. [Full Text] [PDF]

				W Hofmann, B Wappenschmidt, S Berhane, R Schmutzler, and S Scherneck Detection of large rearrangements of exons 13 and 22 in the BRCA1 gene in German families J. Med. Genet., July 1, 2002; 39(7): e36 - 36. [Full Text] [PDF]

				D. M. Euhus, K. C. Smith, L. Robinson, A. Stucky, O. I. Olopade, S. Cummings, J. E. Garber, A. Chittenden, G. B. Mills, P. Rieger, et al. Pretest Prediction of BRCA1 or BRCA2 Mutation by Risk Counselors and the Computer Model BRCAPRO J Natl Cancer Inst, June 5, 2002; 94(11): 844 - 851. [Abstract] [Full Text] [PDF]

				S. M Akrami, R. M Winter, J D. Brook, and J. A L Armour Detection of a large TBX5 deletion in a family with Holt-Oram syndrome J. Med. Genet., December 1, 2001; 38 (12): e44 - e44. [Full Text] [PDF]

				S. Gad, M. T Scheuner, S. Pages-Berhouet, V. Caux-Moncoutier, A. Bensimon, A. Aurias, M. Pinto, and D. Stoppa-Lyonnet Identification of a large rearrangement of the BRCA1 gene using colour bar code on combed DNA in an American breast/ovarian cancer family previously studied by direct sequencing J. Med. Genet., June 1, 2001; 38(6): 388 - 392. [Full Text]

				J. A. L. Armour, C. Sismani, P. C. Patsalis, and G. Cross Measurement of locus copy number by hybridisation with amplifiable probes Nucleic Acids Res., January 15, 2000; 28(2): 605 - 609. [Abstract] [Full Text] [PDF]

				M. Reichel, E. Gillert, I. Breitenlohner, R. Repp, J. Greil, J. D. Beck, G. H. Fey, and R. Marschalek Rapid Isolation of Chromosomal Breakpoints from Patients with t(4;11) Acute Lymphoblastic Leukemia: Implications for Basic and Clinical Research Cancer Res., July 1, 1999; 59(14): 3357 - 3362. [Abstract] [Full Text] [PDF]

				G Goelen, E Teugels, M Bonduelle, B Neyns, and J De Grève High frequency of BRCA1/2 germline mutations in 42 Belgian families with a small number of symptomatic subjects J. Med. Genet., April 1, 1999; 36(4): 304 - 308. [Abstract] [Full Text]

				N. Puget, D. Stoppa-Lyonnet, O. M. Sinilnikova, S. Pages, H. T. Lynch, G. M. Lenoir, and S. Mazoyer Screening for Germ-Line Rearrangements and Regulatory Mutations in BRCA1 Led to the Identification of Four New Deletions Cancer Res., January 1, 1999; 59(2): 455 - 461. [Abstract] [Full Text] [PDF]

				T. S. Frank Hereditary Risk of Breast and Ovarian Carcinoma: The Role of the Oncologist Oncologist, December 1, 1998; 3(6): 403 - 412. [Abstract] [Full Text]

				B. Newman, H. Mu, L. M. Butler, R. C. Millikan, P. G. Moorman, and M.-C. King Frequency of Breast Cancer Attributable to BRCA1 in a Population-Based Series of American Women JAMA, March 25, 1998; 279(12): 915 - 921. [Abstract] [Full Text] [PDF]

				F. J. Couch and L. C. Hartmann BRCA1 Testing--Advances and Retreats JAMA, March 25, 1998; 279(12): 955 - 957. [Full Text] [PDF]

				M. P. Strout, G. Marcucci, C. D. Bloomfield, and M. A. Caligiuri The partial tandem duplication of ALL1 (MLL) is consistently generated by Alu-mediated homologous recombination in acute myeloid leukemia PNAS, March 3, 1998; 95(5): 2390 - 2395. [Abstract] [Full Text] [PDF]

				D. Shattuck-Eidens, A. Oliphant, M. McClure, C. McBride, J. Gupte, T. Rubano, D. Pruss, S. V. Tavtigian, D. H.-F. Teng, N. Adey, et al. BRCA1 Sequence Analysis in Women at High Risk for Susceptibility Mutations: Risk Factor Analysis and Implications for Genetic Testing JAMA, October 15, 1997; 278(15): 1242 - 1250. [Abstract] [PDF]