The Occurrence and Contribution of Germline BRCA1/2 Sequence Alterations in Iranian Patients With Breast Cancer
Background: Breast cancer is the most common form of hereditary cancer worldwide and is an important cause of morbidity and mortality. Approximately 5-10% of breast and ovarian cancers are due to the highly penetrating germline mutations in cancer predisposing genes. Two genes, BRCA1 and BRCA2, acco...
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doaj-ef7ce24c0e8e4798a4df7cfeef329d992020-11-24T23:21:46ZfasTehran University of Medical SciencesTehran University Medical Journal1683-17641735-73222011-12-01699559570The Occurrence and Contribution of Germline BRCA1/2 Sequence Alterations in Iranian Patients With Breast CancerZeinali SSharafi Farzad MSharifi ZVahidi MShahab Movahead ZHarriry ZSalehi RFallah MSSirati FNafissi NKeshavarzi FBackground: Breast cancer is the most common form of hereditary cancer worldwide and is an important cause of morbidity and mortality. Approximately 5-10% of breast and ovarian cancers are due to the highly penetrating germline mutations in cancer predisposing genes. Two genes, BRCA1 and BRCA2, account for at least half of these cases. The demand for BRCA1 and BRCA2 mutation screening is rapidly increasing as their identification will affect the medical management of people at increased risk for the disease. Therefore, the aim of this study was to investigate BRCA1/2 mutations in 100 high risk Iranian families.Methods: One hundred families who met the minimal risk factors for breast/ovarian cancer were screened among the families referred to Kawsar Human Genetics Research Center for the diseases in 2009-2011. The entire coding sequences and each intron/exon boundaries of BRCA1/2 genes were screened for by direct sequencing and MLPA in both patients and the controls.Results: In the present study, we could detect the following novel mutations: p.Gly1140Ser, p.Ile26Val, p.Leu1418X, p.Glu23Gln, p.Leu3X, p.Asn1403His, p.Asn1403Asp, p.Lys581X, p.Pro938Arg, p.Thr77Arg, p.Leu6Val, p.Arg7Cys, p.Leu15Ile, p.Ser177Thr, IVS7+83(-TT), IVS8 -70(-CATT), IVS2+9(G>C), IVS1-20(G>A), IVS1-8(A>G), p.Met1Ile, IVS2+24(A>G), IVS5-8 (A>G), IVS2(35-39)TTcctatGAT, IVS13+9 G>C in BRCA1 and p.Glu1391Gly, p. Val1852Ile, IVS6-70(T>G), 1994-1995 (InsA) in BRCA2.Conclusion: Ten mutations seemed to be pathogenic and the disease-causing mutations were seen in 16% of the families. In addition, from the total number of substitutions and reassortments (42), 80% related to BRCA1 and 20% to mutations in BRCA2 genes.http://journals.tums.ac.ir/PdfMed.aspx?pdf_med=/upload_files/pdf/19562.pdf&manuscript_id=19562BRCA1/ GenesBreast CancerFamilial CancerIran |
collection |
DOAJ |
language |
fas |
format |
Article |
sources |
DOAJ |
author |
Zeinali S Sharafi Farzad M Sharifi Z Vahidi M Shahab Movahead Z Harriry Z Salehi R Fallah MS Sirati F Nafissi N Keshavarzi F |
spellingShingle |
Zeinali S Sharafi Farzad M Sharifi Z Vahidi M Shahab Movahead Z Harriry Z Salehi R Fallah MS Sirati F Nafissi N Keshavarzi F The Occurrence and Contribution of Germline BRCA1/2 Sequence Alterations in Iranian Patients With Breast Cancer Tehran University Medical Journal BRCA1/ Genes Breast Cancer Familial Cancer Iran |
author_facet |
Zeinali S Sharafi Farzad M Sharifi Z Vahidi M Shahab Movahead Z Harriry Z Salehi R Fallah MS Sirati F Nafissi N Keshavarzi F |
author_sort |
Zeinali S |
title |
The Occurrence and Contribution of Germline BRCA1/2 Sequence Alterations in Iranian Patients With Breast Cancer |
title_short |
The Occurrence and Contribution of Germline BRCA1/2 Sequence Alterations in Iranian Patients With Breast Cancer |
title_full |
The Occurrence and Contribution of Germline BRCA1/2 Sequence Alterations in Iranian Patients With Breast Cancer |
title_fullStr |
The Occurrence and Contribution of Germline BRCA1/2 Sequence Alterations in Iranian Patients With Breast Cancer |
title_full_unstemmed |
The Occurrence and Contribution of Germline BRCA1/2 Sequence Alterations in Iranian Patients With Breast Cancer |
title_sort |
occurrence and contribution of germline brca1/2 sequence alterations in iranian patients with breast cancer |
publisher |
Tehran University of Medical Sciences |
series |
Tehran University Medical Journal |
issn |
1683-1764 1735-7322 |
publishDate |
2011-12-01 |
description |
Background: Breast cancer is the most common form of hereditary cancer worldwide and is an important cause of morbidity and mortality. Approximately 5-10% of breast and ovarian cancers are due to the highly penetrating germline mutations in cancer predisposing genes. Two genes, BRCA1 and BRCA2, account for at least half of these cases. The demand for BRCA1 and BRCA2 mutation screening is rapidly increasing as their identification will affect the medical management of people at increased risk for the disease. Therefore, the aim of this study was to investigate BRCA1/2 mutations in 100 high risk Iranian families.Methods: One hundred families who met the minimal risk factors for breast/ovarian cancer were screened among the families referred to Kawsar Human Genetics Research Center for the diseases in 2009-2011. The entire coding sequences and each intron/exon boundaries of BRCA1/2 genes were screened for by direct sequencing and MLPA in both patients and the controls.Results: In the present study, we could detect the following novel mutations: p.Gly1140Ser, p.Ile26Val, p.Leu1418X, p.Glu23Gln, p.Leu3X, p.Asn1403His, p.Asn1403Asp, p.Lys581X, p.Pro938Arg, p.Thr77Arg, p.Leu6Val, p.Arg7Cys, p.Leu15Ile, p.Ser177Thr, IVS7+83(-TT), IVS8 -70(-CATT), IVS2+9(G>C), IVS1-20(G>A), IVS1-8(A>G), p.Met1Ile, IVS2+24(A>G), IVS5-8 (A>G), IVS2(35-39)TTcctatGAT, IVS13+9 G>C in BRCA1 and p.Glu1391Gly, p. Val1852Ile, IVS6-70(T>G), 1994-1995 (InsA) in BRCA2.Conclusion: Ten mutations seemed to be pathogenic and the disease-causing mutations were seen in 16% of the families. In addition, from the total number of substitutions and reassortments (42), 80% related to BRCA1 and 20% to mutations in BRCA2 genes. |
topic |
BRCA1/ Genes Breast Cancer Familial Cancer Iran |
url |
http://journals.tums.ac.ir/PdfMed.aspx?pdf_med=/upload_files/pdf/19562.pdf&manuscript_id=19562 |
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