Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Oct 16:1:14012.
doi: 10.1038/hgv.2014.12. eCollection 2014.

Germline mutations in BRCA1, BRCA2, CHEK2 and TP53 in patients at high-risk for HBOC: characterizing a Northeast Brazilian Population

Gabriela Es Felix  1 , Camila Abe-Sandes  2 , Taísa Mb Machado-Lopes  2 , Thaís F Bomfim  2 , Rodrigo Santa Cruz Guindalini  3 , Vanessa Catarine Sar Santos  2 , Lorena Meyer  2 , Polyanna C Oliveira  1 , João Cláudio Neiva  2 , Roberto Meyer  2 , Maura Romeo  2 , Maria Betânia Toralles  2 , Ivana Nascimento  2 , Kiyoko Abe-Sandes  1
Affiliations

Germline mutations in BRCA1, BRCA2, CHEK2 and TP53 in patients at high-risk for HBOC: characterizing a Northeast Brazilian Population

Gabriela Es Felix et al. Hum Genome Var. .

Abstract

Considering the importance of BRCA1, BRCA2, CHEK2 and TP53 in the development of hereditary early-onset breast and ovarian cancer and that the genetic susceptibility profile of the Northeast population from Brazil has never been analyzed, this study aimed to verify the frequency of mutations of clinical significance in these genes in high-risk hereditary breast and ovarian cancer (HBOC) syndrome patients from that region. DNA samples from 106 high-risk unrelated patients mostly from Bahia, the biggest state in the Northeast region, were analyzed. These patients underwent full BRCA1 gene sequencing, screening for common founder mutations in the BRCA2, CHEK2 and TP53 genes and genetic ancestry analysis with nine ancestry informative markers. The positive results were confirmed by two sequencing reactions. Three mutations of clinical significance were found: BRCA1 p.R71G (4.71%), 3450del4 (3.77%) and TP53 p.R337H (0.94%). The genetic ancestry analysis showed a high European ancestry contribution (62.2%) as well as considerable African (31.2%) and Amerindian (6.6%) ancestry contributions (r (2)=0.991); this degree of heterogeneity was also significant in the population structure analysis (r=0.604). This population is highly admixed with a different spectrum of genetic susceptibility, with the Galician founder mutation BRCA1 p.R71G accounting for 50% of all identified mutations in high-risk HBOC patients. TP53 p.R337H was also significantly frequent; thus, the combined screening of BRCA1/2 and TP53 should be offered to high-risk HBOC patients from Northeast Brazil.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Distribution of the subjects according their estimated ancestral background (triangle plot) and population structure for the trihybrid model (bar plot). Note: red dots, African population; green dots, Amerindian subjects; blue, European subjects; yellow dots, Brazilian population (study population).
Figure 2
Figure 2
Sequencing fragments of carriers and noncarriers for the BRCA1 p.R71G, BRCA1 3450del4 and TP53 p.R337H mutations. Note: Het, heterozygous type; Wt, wild type.
Figure 3
Figure 3
Pedigree of families harboring the BRCA1 p.R71G, BRCA1 3450del4 and TP53 p.R337H mutations. Note: positive (+) symbol, mutation carrier; negative (−) symbol, noncarrier; *age unknown. The numbers between parentheses represent the age at diagnosis in years.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global Cancer Statistics. CA Cancer J Clin 2011; 61: 69–90. - PubMed
    1. Smith EC. An overview of hereditary breast and ovarian cancer syndrome. J Midwifery Womens Health 2012; 57: 577–584. - PubMed
    1. Apoustolou P, Fostira F. Hereditary breast cancer: the era of new susceptibility genes. Biomed Res Int 2013; 2013: 74318. - PMC - PubMed
    1. Achatz MIW, Olivier M, Le Calvez F, Martel-Planche G, Lopes A, Rossi BM et al. The TP53 mutation, R337H, is associated with Li–Fraumeni and Li–Fraumeni-like syndromes in Brazilian families. Cancer Lett 2007; 245: 96–102. - PubMed
    1. Allinen M M, Huusko P, Mäntyniemi S, Launonen V, Winqvist R. Mutation analysis of the CHEK2 gene in families with hereditary breast cancer. Br J Cancer 2001; 85: 209–212. - PMC - PubMed