Breast Cancer Research and Treatment

, Volume 126, Issue 3, pp 705–716 | Cite as

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

  • Patricio Gonzalez-Hormazabal
  • Sara Gutierrez-Enriquez
  • Daniel Gaete
  • Jose M. Reyes
  • Octavio Peralta
  • Enrique Waugh
  • Fernando Gomez
  • Sonia Margarit
  • Teresa Bravo
  • Rafael Blanco
  • Orland Diez
  • Lilian Jara


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.


Breast cancer BRCA1/2 Chilean population LGRs Recurrent mutations 


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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Patricio Gonzalez-Hormazabal
    • 1
  • Sara Gutierrez-Enriquez
    • 2
    • 3
  • Daniel Gaete
    • 1
  • Jose M. Reyes
    • 4
  • Octavio Peralta
    • 4
    • 5
  • Enrique Waugh
    • 6
  • Fernando Gomez
    • 6
  • Sonia Margarit
    • 7
  • Teresa Bravo
    • 8
  • Rafael Blanco
    • 1
  • Orland Diez
    • 2
    • 9
  • Lilian Jara
    • 1
  1. 1.Human Genetics Program, Institute of Biomedical Sciences (ICBM), School of MedicineUniversity of ChileSantiagoChile
  2. 2.Vall d’Hebron Institute of Oncology (VHIO)BarcelonaSpain
  3. 3.Medical Oncology ProgramVall d’Hebron University Hospital Research InstituteBarcelonaSpain
  4. 4.Clínica Las CondesSantiagoChile
  5. 5.Department of Ginaecology and Obstetrics, School of MedicineUniversity of ChileSantiagoChile
  6. 6.Clínica Santa MaríaSantiagoChile
  7. 7.School of Medicine and Clínica AlemanaUniversidad del DesarrolloSantiagoChile
  8. 8.National Cancer Society (Corporación Nacional del Cáncer—CONAC)SantiagoChile
  9. 9.Oncogenetics Laboratory, Molecular Medicine and Genetics ProgramUniversity Hospital Vall d’HebronBarcelonaSpain

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