# Genetic testing for BRCA1/2 variants in Northern African women with ovarian and breast cancers: a multicentre study of an under-represented ancestry

## TL;DR

This study examines BRCA1/2 genetic variants in Northern African women with ovarian and breast cancers, revealing unique patterns and the feasibility of genetic testing in resource-limited settings.

## Contribution

The study provides new insights into BRCA1/2 variant frequencies and patterns specific to Northern African ancestry, previously under-represented in genetic research.

## Key findings

- BRCA1/2 pathogenic variants were found in 18.8% of patients, with similar rates to Western populations.
- Northern African ancestry showed unique BRCA2 variant patterns not seen in other populations.
- A bioinformatic framework reclassified 60% of variants of uncertain significance.

## Abstract

There is a lack of studies investigating the burden of BRCA1/2 pathogenic variants (PVs) in Northern African countries using next-generation sequencing (NGS)-based testing in patients with epithelial ovarian (EOC) and triple-negative breast cancer (TNBC).

We established a multicentre registry for genetic testing of unselected patients referred from five centres from 2019 to 2022 across Egypt. Germline or somatic BRCA1/2 sequencing was carried out by target enrichment using the AmoyDx® BRCA1/2 Mutation Kit, and sequencing was carried out using the Illumina NextSeq500 system.

Genetic testing was successfully carried out for 1349 of 1420 (95%) patients tested (EOC = 1031, TNBC = 318). The median age was 55 years (range 20-86 years). We identified 258 BRCA1/2 PVs affecting 254 (18.8%) patients. The rate of BRCA1/2 PVs in EOC and TNBC was 18.2% and 20.8%, respectively. Although the rate of PVs in our cohort was similar to the Western cancer population, there were significant differences in the enrichment at the variant level. The majority of recurrent BRCA2 PVs, but not BRCA1 PVs, were breast or ovarian lineage-unique. We developed a limited-resource conscious framework that provided a reclassification of 60% of identified variants of uncertain significance (VUS).

Our findings would help to enhance cancer care and enrich the genetic epidemiology of women from such understudied ancestries.

•Central NGS testing was feasible in resource-limited settings, with rates similar to those observed in Western populations.•Women of Northern African ancestry exhibited unique BRCA1/2 variation patterns that differed from other ancestries.•A resource-conscious bioinformatic framework enabled reclassification of 60% of the identified VUS.

Central NGS testing was feasible in resource-limited settings, with rates similar to those observed in Western populations.

Women of Northern African ancestry exhibited unique BRCA1/2 variation patterns that differed from other ancestries.

A resource-conscious bioinformatic framework enabled reclassification of 60% of the identified VUS.