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Spectrum of BRCA1/2 point mutations and genomic rearrangements in high-risk breast/ovarian cancer Chilean families

  • Epidemiology
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Abstract

The distribution of BRCA1/2 germline mutations in breast/ovarian cancer (BC/OC) families varies among different populations. In the Chilean population, there are only two reports of mutation analysis of BRCA1/2, and these included a low number of BC and/or OC patients. Moreover, the prevalence of BRCA1/2 genomic rearrangements in Chilean and in other South American populations is unknown. In this article, we present the mutation-detection data corresponding to a set of 326 high-risk families analyzed by conformation-sensitive gel electrophoresis and heteroduplex analysis. To determine the contribution of BRCA1/2 LGRs in Chilean BC patients, we analyzed 56 high-risk subjects with no pathogenic BRCA1/2 point mutations. Germline BRCA1/2 point mutations were found in 23 (7.1%) of the 326 Chilean families. Families which had at least three BC and/or OC cases showed the highest frequency of mutations (15.9%). We identified 14 point pathogenic mutations. Three recurrent mutations in BRCA1 (c.187_188delAG, c.2605_2606delTT, and c.3450_3453delCAAG) and three in BRCA2 (c.4969_4970insTG, c.5374_5377delTATG, and c.6503_6504delTT) contributed to 63.6 and 66.7% of all the deleterious mutations of each gene, which may reflect the presence of region-specific founder effects. Taken together BRCA1/2 recurrent point mutations account for 65.2% (15/23) of the BRCA1/2 (+) families. No large deletions or duplications involving BRCA1/2 were identified in a subgroup of 56 index cases negative for BRCA1/2 point mutations. Our study, which is the largest conducted to date in a South American population, provides a comprehensive analysis on the type and distribution of BRCA1/2 mutations and allelic variants.

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Acknowledgments

The authors thank the many families who participated in the research studies described in this article. We acknowledge the Breast Cancer Group of CONAC: Maria Teresa Barrios, Angelica Soto, Rossana Recabbarren, and Leticia Garcia; and Lorena Seccia for her technical assistance. We also acknowledge the financial support of Vicerrectoria de Investigacion y Desarrollo (VID) Universidad de Chile (ENL 10/04) and Corporacion Nacional del Cancer (CONAC). This study has been partially supported by a UICC International Cancer Technology Transfer Fellowship (ICR/08/152) and with Federal funds from the National Cancer Institute, National Institutes of Health under Contract NO2-CO-41101, and partially supported by a grant of the “Fondo de Investigación Sanitaria” from the Spanish Health Ministry: FIS 05/2181.

Conflict of interest

The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Human Genetics Program, Institute of Biomedical Sciences (ICBM), School of Medicine, University of Chile, Av. Independencia 1027, P.O. Box 70061, Santiago, Chile

    Patricio Gonzalez-Hormazabal, Daniel Gaete, Rafael Blanco & Lilian Jara

  2. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

    Sara Gutierrez-Enriquez & Orland Diez

  3. Medical Oncology Program, Vall d’Hebron University Hospital Research Institute, Barcelona, Spain

    Sara Gutierrez-Enriquez

  4. Clínica Las Condes, Santiago, Chile

    Jose M. Reyes & Octavio Peralta

  5. Department of Ginaecology and Obstetrics, School of Medicine, University of Chile, Av Santa Rosa 1234, Santiago, Chile

    Octavio Peralta

  6. Clínica Santa María, Santiago, Chile

    Enrique Waugh & Fernando Gomez

  7. School of Medicine and Clínica Alemana, Universidad del Desarrollo, Santiago, Chile

    Sonia Margarit

  8. National Cancer Society (Corporación Nacional del Cáncer—CONAC), Santiago, Chile

    Teresa Bravo

  9. Oncogenetics Laboratory, Molecular Medicine and Genetics Program, University Hospital Vall d’Hebron, Passeig Vall d’Hebron 119-129, 08035, Barcelona, Spain

    Orland Diez

Authors
  1. Patricio Gonzalez-Hormazabal
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  2. Sara Gutierrez-Enriquez
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  3. Daniel Gaete
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  4. Jose M. Reyes
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  5. Octavio Peralta
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  6. Enrique Waugh
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  7. Fernando Gomez
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  8. Sonia Margarit
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  9. Teresa Bravo
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  10. Rafael Blanco
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  11. Orland Diez
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  12. Lilian Jara
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Corresponding authors

Correspondence to Orland Diez or Lilian Jara.

Additional information

Orland Diez and Lilian Jara contributed equally to this study.

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Gonzalez-Hormazabal, P., Gutierrez-Enriquez, S., Gaete, D. et al. Spectrum of BRCA1/2 point mutations and genomic rearrangements in high-risk breast/ovarian cancer Chilean families. Breast Cancer Res Treat 126, 705–716 (2011). https://doi.org/10.1007/s10549-010-1170-y

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  • DOI: https://doi.org/10.1007/s10549-010-1170-y

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