BRCA1 and BRCA2 founder mutations account for 78% of germline carriers among hereditary breast cancer families in Chile

Identifying founder mutations in BRCA1 and BRCA2 in specific populations constitute a valuable opportunity for genetic screening. Several studies from different populations have reported recurrent and/or founder mutations representing a relevant proportion of BRCA mutation carriers. In Latin America, only few founder mutations have been described. We screened 453 Chilean patients with hereditary breast cancer for mutations in BRCA1 and BRCA2. For recurrent mutations, we genotyped 11 microsatellite markers in BRCA1 and BRCA2 in order to determine a founder effect through haplotype analysis. We found a total of 25 mutations (6 novel) in 71 index patients among which, nine are present exclusively in Chilean patients. Our analysis revealed the presence of nine founder mutations, 4 in BRCA1 and 5 in BRCA2, shared by 2 to 10 unrelated families and spread in different regions of Chile. Our panel contains the highest amount of founder mutations until today and represents the highest percentage (78%) of BRCA1 and BRCA2 mutation carriers. We suggest that the dramatic reduction of Amerindian population due to smallpox and wars with Spanish conquerors, a scarce population increase during 300 years, and the geographic position of Chile constituted a favorable scenario to establish founder genetic markers in our population.

• Publication year

  2017

• Venue

  OncoTarget

• Publication date

  2017-06-29

• Fields of study

  Geography, Medicine

• Identifiers
  DOI 10.18632/oncotarget.18815PMID 29088781PMCID 5650336
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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  2015cited by this paper
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  2015cited by this paper
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  2013cited by this paper
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  2013influential reference
• BRCA1 And BRCA2 analysis of Argentinean breast/ovarian cancer patients selected for age and family history highlights a role for novel mutations of putative south-American origin

  2012influential reference
• BRCA1 and BRCA2 mutations in breast cancer patients from Venezuela.

  2012cited by this paper
• Predicting the Functional Effect of Amino Acid Substitutions and Indels

  2012cited by this paper
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  2011cited by this paper
• Spectrum of BRCA1/2 point mutations and genomic rearrangements in high-risk breast/ovarian cancer Chilean families

  2011influential reference
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  2010cited by this paper
• A method and server for predicting damaging missense mutations

  2010cited by this paper
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  2009cited by this paper
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  2008cited by this paper
• Functional assays for classification of BRCA2 variants of uncertain significance.

  2008cited by this paper
• ACMG recommendations for standards for interpretation and reporting of sequence variations: Revisions 2007

  2008cited by this paper
• Genetic analysis of BRCA1 and BRCA2 in breast/ovarian cancer families from Aragon (Spain): two novel truncating mutations and a large genomic deletion in BRCA1

  2008cited by this paper
• Breast cancer risk associated with BRCA1 and BRCA2 in diverse populations

  2007cited by this paper
• Founder mutations in BRCA1 and BRCA2 genes.

  2007cited by this paper
• High proportion of BRCA1/2 founder mutations in Hispanic breast/ovarian cancer families from Colombia

  2007influential reference
• Prevalence of BRCA1 and BRCA2 mutations in breast cancer patients from Brazil

  2007influential reference
• High proportion of novel mutations ofBRCA1 andBRCA2 in breast/ovarian cancer patients from Castilla-León (central Spain)

  2006cited by this paper
• BRCA1 and BRCA2 mutations in a South American population.

  2006cited by this paper
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  2005cited by this paper
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  2005cited by this paper
• Incidence of BRCA1 and BRCA2 mutations in 54 Chilean families with breast/ovarian cancer, genotype–phenotype correlations

  2005influential reference
• A high proportion of founder BRCA1 mutations in Polish breast cancer families

  2004cited by this paper
• A comparison of bayesian methods for haplotype reconstruction from population genotype data.

  2003cited by this paper
• [Genetic composition of the Chilean population. Analysis of mitochondrial DNA polymorphism].

  2002cited by this paper
• BRCA1 and BRCA2 mutation analysis of early‐onset and familial breast cancer cases in Mexico

  2002influential reference
• Espagnols d'outre-mer : émigration, métissage et reproduction sociale à Santiago du Chili, au XVIIe siècle

  2002cited by this paper
• A new statistical method for haplotype reconstruction from population data.

  2001cited by this paper
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  2001cited by this paper
• The R71G BRCA1 is a founder Spanish mutation and leads to aberrant splicing of the transcript

  2001cited by this paper
• Study of a single BRCA2 mutation with high carrier frequency in a small population.

  1997cited by this paper
• Founder BRCA1 and BRCA2 mutations in Ashkenazi Jews in Israel: frequency and differential penetrance in ovarian cancer and in breast-ovarian cancer families.

  1997cited by this paper
• High prevalence of the 999del5 mutation in icelandic breast and ovarian cancer patients.

  1996cited by this paper
• A single BRCA2 mutation in male and female breast cancer families from Iceland with varied cancer phenotypes

  1996cited by this paper
• Identification of the breast cancer susceptibility gene BRCA2

  1996cited by this paper
• Identification of the breast cancer susceptibility gene BRCA2

  1995cited by this paper
• A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1.

  1994cited by this paper
• A rapid non-enzymatic method for the preparation of HMW DNA from blood for RFLP studies.

  1991influential reference
• Bioinformatics Applications Note Databases and Ontologies Deriving the Consequences of Genomic Variants with the Ensembl Api and Snp Effect Predictor

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  2025cites this paper
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