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Breast Cancer Research and Treatment

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08.11.2016 | Preclinical study

Contribution of BRCA1 large genomic rearrangements to early-onset and familial breast/ovarian cancer in Pakistan

verfasst von: Muhammad U. Rashid, Noor Muhammad, Asim Amin, Asif Loya, Ute Hamann

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 2/2017

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Abstract

Background

Germline mutations in BRCA1 and BRCA2 (BRCA1/2) account for the majority of hereditary breast and/or ovarian cancers. Pakistan has one of the highest rates of breast cancer incidence in Asia, where BRCA1/2 small-range mutations account for 17% of early-onset and familial breast/ovarian cancer patients. We report the first study from Pakistan evaluating the prevalence of BRCA1/2 large genomic rearrangements (LGRs) in breast and/or ovarian cancer patients who do not harbor small-range BRCA1/2 mutations.

Materials and methods

Both BRCA1/2 genes were comprehensively screened for LGRs using multiplex ligation-dependent probe amplification in 120 BRCA1/2 small-range mutations negative early-onset or familial breast/ovarian cancer patients from Pakistan (Group 1). The breakpoints were characterized by long-range PCR- and DNA-sequencing analyses. An additional cohort of 445 BRCA1/2 negative high-risk patients (Group 2) was analyzed for the presence of LGRs identified in Group 1.

Results

Three different BRCA1 LGRs were identified in Group 1 (4/120; 3.3%), two of these were novel. Exon 1–2 deletion was observed in two unrelated patients: an early-onset breast cancer patient and another bilateral breast cancer patient from a hereditary breast cancer (HBC) family. Novel exon 20–21 deletion was detected in a 29-year-old breast cancer patient from a HBC family. Another novel exon 21–24 deletion was identified in a breast-ovarian cancer patient from a hereditary breast and ovarian cancer family. The breakpoints of all deletions were characterized. Screening of the 445 patients in Group 2 for the three LGRs revealed ten additional patients harboring exon 1–2 deletion or exon 21–24 deletion (10/445; 2.2%). No BRCA2 LGRs were identified.

Conclusions

LGRs in BRCA1 are found with a considerable frequency in Pakistani breast/ovarian cancer cases. Our findings suggest that BRCA1 exons 1–2 deletion and exons 21–24 deletion should be included in the recurrent BRCA1/2 mutations panel for genetic testing of high-risk Pakistani breast/ovarian cancer patients.

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Titel: Contribution of BRCA1 large genomic rearrangements to early-onset and familial breast/ovarian cancer in Pakistan
verfasst von: Muhammad U. Rashid
Noor Muhammad
Asim Amin
Asif Loya
Ute Hamann
Publikationsdatum: 08.11.2016
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 2/2017
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-016-4044-0

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Contribution of BRCA1 large genomic rearrangements to early-onset and familial breast/ovarian cancer in Pakistan

Abstract

Background

Materials and methods

Results

Conclusions

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Abstract

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Materials and methods

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