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Familial Cancer

, Volume 13, Issue 3, pp 437–444 | Cite as

BRCA1 point mutations in premenopausal breast cancer patients from Central Sudan

  • Ida Biunno
  • Gitana Aceto
  • Khalid Dafaallah Awadelkarim
  • Annalisa Morgano
  • Ahmed Elhaj
  • Elgaylani Abdalla Eltayeb
  • Dafalla Omer Abuidris
  • Nasr Eldin Elwali
  • Chiara Spinelli
  • Pasquale De Blasio
  • Ermanna Rovida
  • Renato Mariani-CostantiniEmail author
Original Article

Abstract

Premenopausal breast cancer (BC) is one of the most common cancers of women in rural Africa and part of the disease load may be related to hereditary predisposition, including mutations in the BRCA1 gene. However, the BRCA1 mutations associated with BC in Africa are scarcely characterized. We report here 33 BRCA1 point mutations, among which 2 novel missense variants, found in 59 Central Sudanese premenopausal BC patients. The high fractions of mutations with intercontinental and uniquely African distribution (17/33, 51.5 % and 14/33, 42.4 %, respectively) are in agreement with the high genetic diversity expected in an African population. Overall 24/33 variants (72.7 %) resulted neutral; 8/33 of unknown significance (24.3 %, including the 2 novel missense mutations); 1 (3.0 %) overtly deleterious. Notably, in silico studies predict that the novel C-terminal missense variant c.5090G>A (p.Cys1697Tyr) affects phosphopeptide recognition by the BRCA1 BRCT1 domain and may have a pathogenic impact. Genetic variation and frequency of unique or rare mutations of uncertain clinical relevance pose significant challenges to BRCA1 testing in Sudan, as it might happen in other low-resource rural African contexts.

Keywords

BRCA1 Breast cancer Sudan Africa Germline mutations Premenopausal 

Notes

Acknowledgments

Supported by Fondazione Cassa di Risparmio della Provincia di Chieti, Chieti, Italy (RMC, KDA, AM). KDA was also sustained by the Sudanese Federal Ministry of Higher Education and Scientific Research, project: Molecular Subtypes and Risk Factors of Breast Cancer in Sudan. RMC acknowledges funding from Ministero Istruzione Università e Ricerca (MIUR), “60 %”, IB and PDB from MIUR FIRB:RBIPO64CRT-005.

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Ida Biunno
    • 1
    • 2
  • Gitana Aceto
    • 3
  • Khalid Dafaallah Awadelkarim
    • 4
  • Annalisa Morgano
    • 5
    • 6
  • Ahmed Elhaj
    • 7
  • Elgaylani Abdalla Eltayeb
    • 7
  • Dafalla Omer Abuidris
    • 7
  • Nasr Eldin Elwali
    • 8
  • Chiara Spinelli
    • 9
  • Pasquale De Blasio
    • 9
  • Ermanna Rovida
    • 1
  • Renato Mariani-Costantini
    • 5
    • 6
    Email author
  1. 1.Institute for Genetic and Biomedical ResearchNational Research CouncilMilanItaly
  2. 2.MultiMedica Science and Technology PoleMilanItaly
  3. 3.Department of Biomedical SciencesG. d’Annunzio UniversityChietiItaly
  4. 4.Department of Molecular Biology, National Cancer Institute (NCI-UG)University of GeziraWad MedaniSudan
  5. 5.Department of Medical, Oral and Biotechnological SciencesG. d’Annunzio UniversityChietiItaly
  6. 6.Unit of General Pathology, Aging Research Center (CeSI)G. d’Annunzio University FoundationChietiItaly
  7. 7.Department of Oncology, National Cancer Institute (NCI-UG)University of GeziraWad MedaniSudan
  8. 8.Department of BiochemistryImam Muhammad bin Saud Islamic UniversityRiyadhSaudi Arabia
  9. 9.Integrated Systems Engineering s.r.lMilanItaly

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