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BRCA1 and BRCA2 germline mutations in 85 Iranian breast cancer patients

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Abstract

Breast cancer is the most common cancer in Iranian women (Mousavi et al in Asian Pac J Cancer Prev 9(2):275–278, 2008). Genetic predisposition accounts for 15% of all breast cancers and germline mutations in breast cancer susceptibility genes, BRCA1 and BRCA2 are responsible for a substantial proportion of high-risk breast and breast/ovarian cancer families (Collaborative Group on Hormonal Factors in Breast Cancer in Lancet 350:1047–1059, 1997; Lee et al in Int Nurs Rev 55:355–359, 2008; Hulka and Stark in Lancet 346:883–887, 1995; Kelsey in Epidemiol Rev 15:256–263, 1993; Tischer et al in J Biol Chem 266:11947–11954, 1991; Newman et al in: Proc Natl Acad Sci USA 85:3044–3048, 1988). Therefore, the aim of this study was to investigate mutations of BRCA1/2 in high risk Iranian families. We screened 85 patients who met our minimal criteria. The entire coding sequences and each intron/exon boundaries of BRCA1/2 genes were screened by direct sequencing. In the present study, we could detect the novel following mutations: p.Glu1735 p.Gly1140Ser, p.Ile26Val, p.Leu1418X, p.Glu23Gln, p.Leu3X, p.Asn1403His, p.Lys581X, p.Pro938Arg, p.Thr77Arg, p.Arg7Cys, p.Ser177Thr, IVS7+83(TT), IVS8−70(-CATT), IVS2+9(-GC), IVS1−20(-GA), IVS1−8(-AG), IVS2+24(AG), IVS5−8 (A–G), IVS2(35–39)TTcctatGAT in BRCA1 and p.Glu1391Gly, 1994_1995 (Ins A), IVS6-70−T>G in BRCA2. In agreement with findings in other populations, we found that family history is a good predictor of being a mutation carrier. Five pathogenic BRCA1 mutations and one pathogenic BRCA2 mutation were detected in 85 index cases.

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Abbreviations

BRCA :

Breast cancer susceptibility gene

μl:

Micro liters

ABI:

Applied Biosystems Inc.

BIC:

Breast Cancer Information Core

HGMD:

The Human Gene Mutation Database at the Institute of Medical Genetics in Cardiff

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Acknowledgments

We thank the patients and their family members for cooperation. This work was supported by Genetics Laboratory of Dr. Zeinali, Kawsar Human Genetics Research Center, Tehran, Iran.

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Authors and Affiliations

  1. Department of Biology, Sanandaj Branch, Islamic Azad University, Sanandaj, Iran

    Fatemeh Keshavarzi

  2. Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran

    Gholam Reza Javadi

  3. Kawsar Human Genetics Research Center, Medical Genetics Laboratory of Dr. Zeinali, P.O. Box 15956445513, Tehran, Iran

    Sirous Zeinali

  4. Pasteur Institute, Tehran, Iran

    Sirous Zeinali

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  1. Fatemeh Keshavarzi
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  2. Gholam Reza Javadi
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  3. Sirous Zeinali
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Correspondence to Sirous Zeinali.

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Keshavarzi, F., Javadi, G.R. & Zeinali, S. BRCA1 and BRCA2 germline mutations in 85 Iranian breast cancer patients. Familial Cancer 11, 57–67 (2012). https://doi.org/10.1007/s10689-011-9477-3

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