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Introduction <p>Germline <i>BRCA1/2</i> (<i>gBRCA1/2</i>) variants are strongly associated with hereditary cancers, and screening for these variants in high-risk populations is recommended for personalized management. This study aims to comprehensively characterize <i>gBRCA1/2</i> variants in cancer and family screening cohorts from the Dubai Emirate, UAE.</p> Material and methods <p>A total of 443 patients with breast, ovarian, prostate and pancreatic cancer were tested for <i>gBRCA1/2</i> variants from 2017 to 2022 using whole-gene sequencing, and data were analysed using variant interpretation and in-silico prediction tools. All <i>BRCA1/2</i> variants were classified as P/LP or variants of uncertain significance (VUS) according to ACMG guidelines.</p> Results <p>In the cancer cohort, 38 out of 306 patients harboured <i>gBRCA1/2</i> P/LP or VUS variants. Of these, 23 (7.5%) were classified as <i>BRCA1/2</i> P/LP, while 15 (4.9%) were categorized as VUS. These variants were predominantly observed in estrogen receptor-positive/progesterone receptor-positive (ER + /PR +) and triple-negative breast cancer patients. Common <i>BRCA1</i> P/LP variants included deletion frameshift variants (c.4065_4068del, c.68_69delAG, c.3228_3229delAG), an insertion frameshift variant (c.1140dup), and a nonsense variant (c.5251C &gt; T). <i>BRCA2</i> P/LP variants included a nonsense variant (c.5645C &gt; A), a missense variant (c.7007G &gt; A), and a deletion frameshift variant (c.2254_2257del). In the family screening cohort, 14 out of 137 samples harboured <i>BRCA1/2</i> P/LP orVUS. Of these, five (3.6%) were classified as P/LP, while nine (6.6%) were VUS. Pathogenic <i>BRCA1</i> variants included deletions (c.4065_4068del, c.3756_3759del) and a nonsense variant (c.5095C &gt; T), while <i>BRCA2</i> PVs included a deletion frameshift (c.771_775del) and a novel missense variant (c.8377G &gt; A). In both cohorts, novel distinct variants were observed.</p> Conclusion <p><i>gBRCA1/2</i> variant prevalence in cancer and family screening cohorts can serve as beneficial personalized tool for management and treatment of cancer patients. Larger studies from other emirates of UAE will serve as a foundation for robust risk assessment and implementation of treatment and prevention strategies.</p>

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Genetic characterization of BRCA1 and BRCA2 variants in cancer and high-risk family screening cohorts in the UAE population

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月21日

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  • Abeer Arif Abdalla Abutalib Al Ali,
  • Moza Mohamed Alechleh Al Ali,
  • Dalia Mahmoud Abdel-Hamid El-Shourbagy,
  • Syed Hammad Hassan Tirmazy,
  • Imran Mirza,
  • Afsheen Raza,
  • Muhammad Farooq Latif,
  • Hemad Yasaei

摘要

Introduction

Germline BRCA1/2 (gBRCA1/2) variants are strongly associated with hereditary cancers, and screening for these variants in high-risk populations is recommended for personalized management. This study aims to comprehensively characterize gBRCA1/2 variants in cancer and family screening cohorts from the Dubai Emirate, UAE.

Material and methods

A total of 443 patients with breast, ovarian, prostate and pancreatic cancer were tested for gBRCA1/2 variants from 2017 to 2022 using whole-gene sequencing, and data were analysed using variant interpretation and in-silico prediction tools. All BRCA1/2 variants were classified as P/LP or variants of uncertain significance (VUS) according to ACMG guidelines.

Results

In the cancer cohort, 38 out of 306 patients harboured gBRCA1/2 P/LP or VUS variants. Of these, 23 (7.5%) were classified as BRCA1/2 P/LP, while 15 (4.9%) were categorized as VUS. These variants were predominantly observed in estrogen receptor-positive/progesterone receptor-positive (ER + /PR +) and triple-negative breast cancer patients. Common BRCA1 P/LP variants included deletion frameshift variants (c.4065_4068del, c.68_69delAG, c.3228_3229delAG), an insertion frameshift variant (c.1140dup), and a nonsense variant (c.5251C > T). BRCA2 P/LP variants included a nonsense variant (c.5645C > A), a missense variant (c.7007G > A), and a deletion frameshift variant (c.2254_2257del). In the family screening cohort, 14 out of 137 samples harboured BRCA1/2 P/LP orVUS. Of these, five (3.6%) were classified as P/LP, while nine (6.6%) were VUS. Pathogenic BRCA1 variants included deletions (c.4065_4068del, c.3756_3759del) and a nonsense variant (c.5095C > T), while BRCA2 PVs included a deletion frameshift (c.771_775del) and a novel missense variant (c.8377G > A). In both cohorts, novel distinct variants were observed.

Conclusion

gBRCA1/2 variant prevalence in cancer and family screening cohorts can serve as beneficial personalized tool for management and treatment of cancer patients. Larger studies from other emirates of UAE will serve as a foundation for robust risk assessment and implementation of treatment and prevention strategies.