High prevalence of deleterious BRCA1 and BRCA2 germline mutations in arab breast and ovarian cancer patients

Al Joharah Alhuqail, Areej Alzahrani, Hannah Almubarak, Sarah Al-Qadheeb, Lamyaa Alghofaili, Nisreen Almoghrabi, Hamed Alhussaini, Ben Ho Park, Dilek Colak, Bedri Karakas

Research output: Contribution to journalArticle

Abstract

Purpose: The BRCA1 and BRCA2 (BRCA) genes are heavily involved in mammalian cell DNA repair processes. Germline pathogenic mutations in BRCA increase the lifetime risk of developing breast and/or ovarian cancer in women. In the Arabian Peninsula, most breast and ovarian cancers are diagnosed as early-onset cases, some of which may be due to germline variants in BRCA genes. To identify the BRCA germline mutation frequency and spectrum in the Arab breast and ovarian cancers, we have sequenced the protein-coding exons of these genes. Methods: All BRCA coding exons were sequenced using genomic DNA isolated from lymphocytes in 173 Arab breast and ovarian cancer patients by a massively parallel sequencing technology and verified by Sanger sequencing. Results: We identified a total of 17 distinct pathogenic mutations, of which four were novel, in 28 patients; nine out of 108 breast (8.3%) and 19 out of 65 ovarian cancer (29.2%) patients. Thirteen of the 17 mutations were detected in BRCA1 and four mutations were found in BRCA2 gene. Four pathogenic BRCA1 mutations (c.1140dupG, c.4136_4137delCT, c.5095C>T, and c.5530delC) accounted for 54% of all the mutations detected in our patient cohort. Additionally, we identified a likely pathogenic BRCA1 missense variant in two of 108 breast (1.9%) and a BRCA2 missense variant in one of 65 ovarian cancer (1.5%) patients. Conclusions: The overall frequencies of the BRCA germline mutations were 10.2% in breast and 30.7% in ovarian cancer patients. These data shed new light into the prevalence of BRCA mutations in the Arab women population.

Original languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalBreast Cancer Research and Treatment
DOIs
StateAccepted/In press - Jan 2 2018

Fingerprint

Germ-Line Mutation
Ovarian Neoplasms
Breast Neoplasms
BRCA2 Gene
Mutation
Breast
Exons
BRCA1 Gene
High-Throughput Nucleotide Sequencing
Mutation Rate
DNA Repair
Lymphocytes
Technology
DNA
Population
Genes

Keywords

  • BRCA1
  • BRCA2
  • Breast cancer
  • Germline mutations
  • Next-generation sequencing
  • Ovarian cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Alhuqail, A. J., Alzahrani, A., Almubarak, H., Al-Qadheeb, S., Alghofaili, L., Almoghrabi, N., ... Karakas, B. (Accepted/In press). High prevalence of deleterious BRCA1 and BRCA2 germline mutations in arab breast and ovarian cancer patients. Breast Cancer Research and Treatment, 1-8. https://doi.org/10.1007/s10549-017-4635-4

High prevalence of deleterious BRCA1 and BRCA2 germline mutations in arab breast and ovarian cancer patients. / Alhuqail, Al Joharah; Alzahrani, Areej; Almubarak, Hannah; Al-Qadheeb, Sarah; Alghofaili, Lamyaa; Almoghrabi, Nisreen; Alhussaini, Hamed; Park, Ben Ho; Colak, Dilek; Karakas, Bedri.

In: Breast Cancer Research and Treatment, 02.01.2018, p. 1-8.

Research output: Contribution to journalArticle

Alhuqail, AJ, Alzahrani, A, Almubarak, H, Al-Qadheeb, S, Alghofaili, L, Almoghrabi, N, Alhussaini, H, Park, BH, Colak, D & Karakas, B 2018, 'High prevalence of deleterious BRCA1 and BRCA2 germline mutations in arab breast and ovarian cancer patients', Breast Cancer Research and Treatment, pp. 1-8. https://doi.org/10.1007/s10549-017-4635-4
Alhuqail, Al Joharah ; Alzahrani, Areej ; Almubarak, Hannah ; Al-Qadheeb, Sarah ; Alghofaili, Lamyaa ; Almoghrabi, Nisreen ; Alhussaini, Hamed ; Park, Ben Ho ; Colak, Dilek ; Karakas, Bedri. / High prevalence of deleterious BRCA1 and BRCA2 germline mutations in arab breast and ovarian cancer patients. In: Breast Cancer Research and Treatment. 2018 ; pp. 1-8.
@article{ccf0334838e943d987a6748c08b26117,
title = "High prevalence of deleterious BRCA1 and BRCA2 germline mutations in arab breast and ovarian cancer patients",
abstract = "Purpose: The BRCA1 and BRCA2 (BRCA) genes are heavily involved in mammalian cell DNA repair processes. Germline pathogenic mutations in BRCA increase the lifetime risk of developing breast and/or ovarian cancer in women. In the Arabian Peninsula, most breast and ovarian cancers are diagnosed as early-onset cases, some of which may be due to germline variants in BRCA genes. To identify the BRCA germline mutation frequency and spectrum in the Arab breast and ovarian cancers, we have sequenced the protein-coding exons of these genes. Methods: All BRCA coding exons were sequenced using genomic DNA isolated from lymphocytes in 173 Arab breast and ovarian cancer patients by a massively parallel sequencing technology and verified by Sanger sequencing. Results: We identified a total of 17 distinct pathogenic mutations, of which four were novel, in 28 patients; nine out of 108 breast (8.3{\%}) and 19 out of 65 ovarian cancer (29.2{\%}) patients. Thirteen of the 17 mutations were detected in BRCA1 and four mutations were found in BRCA2 gene. Four pathogenic BRCA1 mutations (c.1140dupG, c.4136_4137delCT, c.5095C>T, and c.5530delC) accounted for 54{\%} of all the mutations detected in our patient cohort. Additionally, we identified a likely pathogenic BRCA1 missense variant in two of 108 breast (1.9{\%}) and a BRCA2 missense variant in one of 65 ovarian cancer (1.5{\%}) patients. Conclusions: The overall frequencies of the BRCA germline mutations were 10.2{\%} in breast and 30.7{\%} in ovarian cancer patients. These data shed new light into the prevalence of BRCA mutations in the Arab women population.",
keywords = "BRCA1, BRCA2, Breast cancer, Germline mutations, Next-generation sequencing, Ovarian cancer",
author = "Alhuqail, {Al Joharah} and Areej Alzahrani and Hannah Almubarak and Sarah Al-Qadheeb and Lamyaa Alghofaili and Nisreen Almoghrabi and Hamed Alhussaini and Park, {Ben Ho} and Dilek Colak and Bedri Karakas",
year = "2018",
month = "1",
day = "2",
doi = "10.1007/s10549-017-4635-4",
language = "English (US)",
pages = "1--8",
journal = "Breast Cancer Research and Treatment",
issn = "0167-6806",
publisher = "Springer New York",

}

TY - JOUR

T1 - High prevalence of deleterious BRCA1 and BRCA2 germline mutations in arab breast and ovarian cancer patients

AU - Alhuqail, Al Joharah

AU - Alzahrani, Areej

AU - Almubarak, Hannah

AU - Al-Qadheeb, Sarah

AU - Alghofaili, Lamyaa

AU - Almoghrabi, Nisreen

AU - Alhussaini, Hamed

AU - Park, Ben Ho

AU - Colak, Dilek

AU - Karakas, Bedri

PY - 2018/1/2

Y1 - 2018/1/2

N2 - Purpose: The BRCA1 and BRCA2 (BRCA) genes are heavily involved in mammalian cell DNA repair processes. Germline pathogenic mutations in BRCA increase the lifetime risk of developing breast and/or ovarian cancer in women. In the Arabian Peninsula, most breast and ovarian cancers are diagnosed as early-onset cases, some of which may be due to germline variants in BRCA genes. To identify the BRCA germline mutation frequency and spectrum in the Arab breast and ovarian cancers, we have sequenced the protein-coding exons of these genes. Methods: All BRCA coding exons were sequenced using genomic DNA isolated from lymphocytes in 173 Arab breast and ovarian cancer patients by a massively parallel sequencing technology and verified by Sanger sequencing. Results: We identified a total of 17 distinct pathogenic mutations, of which four were novel, in 28 patients; nine out of 108 breast (8.3%) and 19 out of 65 ovarian cancer (29.2%) patients. Thirteen of the 17 mutations were detected in BRCA1 and four mutations were found in BRCA2 gene. Four pathogenic BRCA1 mutations (c.1140dupG, c.4136_4137delCT, c.5095C>T, and c.5530delC) accounted for 54% of all the mutations detected in our patient cohort. Additionally, we identified a likely pathogenic BRCA1 missense variant in two of 108 breast (1.9%) and a BRCA2 missense variant in one of 65 ovarian cancer (1.5%) patients. Conclusions: The overall frequencies of the BRCA germline mutations were 10.2% in breast and 30.7% in ovarian cancer patients. These data shed new light into the prevalence of BRCA mutations in the Arab women population.

AB - Purpose: The BRCA1 and BRCA2 (BRCA) genes are heavily involved in mammalian cell DNA repair processes. Germline pathogenic mutations in BRCA increase the lifetime risk of developing breast and/or ovarian cancer in women. In the Arabian Peninsula, most breast and ovarian cancers are diagnosed as early-onset cases, some of which may be due to germline variants in BRCA genes. To identify the BRCA germline mutation frequency and spectrum in the Arab breast and ovarian cancers, we have sequenced the protein-coding exons of these genes. Methods: All BRCA coding exons were sequenced using genomic DNA isolated from lymphocytes in 173 Arab breast and ovarian cancer patients by a massively parallel sequencing technology and verified by Sanger sequencing. Results: We identified a total of 17 distinct pathogenic mutations, of which four were novel, in 28 patients; nine out of 108 breast (8.3%) and 19 out of 65 ovarian cancer (29.2%) patients. Thirteen of the 17 mutations were detected in BRCA1 and four mutations were found in BRCA2 gene. Four pathogenic BRCA1 mutations (c.1140dupG, c.4136_4137delCT, c.5095C>T, and c.5530delC) accounted for 54% of all the mutations detected in our patient cohort. Additionally, we identified a likely pathogenic BRCA1 missense variant in two of 108 breast (1.9%) and a BRCA2 missense variant in one of 65 ovarian cancer (1.5%) patients. Conclusions: The overall frequencies of the BRCA germline mutations were 10.2% in breast and 30.7% in ovarian cancer patients. These data shed new light into the prevalence of BRCA mutations in the Arab women population.

KW - BRCA1

KW - BRCA2

KW - Breast cancer

KW - Germline mutations

KW - Next-generation sequencing

KW - Ovarian cancer

UR - http://www.scopus.com/inward/record.url?scp=85039852483&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85039852483&partnerID=8YFLogxK

U2 - 10.1007/s10549-017-4635-4

DO - 10.1007/s10549-017-4635-4

M3 - Article

C2 - 29297111

AN - SCOPUS:85039852483

SP - 1

EP - 8

JO - Breast Cancer Research and Treatment

JF - Breast Cancer Research and Treatment

SN - 0167-6806

ER -