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Frequency of Pathogenic Germline Mutations in Early and Late Onset Familial Breast Cancer Patients Using Multi-Gene Panel Sequencing: An Egyptian Study
Ist Teil von
Genes, 2022-12, Vol.14 (1), p.106
Ort / Verlag
Switzerland: MDPI AG
Erscheinungsjahr
2022
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
Precision oncology has been increasingly used in clinical practice and rapidly evolving in the oncology field. Thus, this study was performed to assess the frequency of germline mutations in early and late onset familial breast cancer (BC) Egyptian patients using multi-gene panel sequencing to better understand the contribution of the inherited germline mutations in BC predisposition. Moreover, to determine the actionable deleterious mutations associated with familial BC that might be used as biomarker for early cancer detection.
Whole blood samples were collected from 101 Egyptian patients selected for BC family history, in addition to 50 age-matched healthy controls. A QIAseq targeted DNA panel (human BC panel) was used to assess the frequency of germline mutations.
A total of 58 patients (57.4%) out of 101 were found to have 27 deleterious germline mutations in 11 cancer susceptibility genes. Of them, 32 (31.6%) patients carried more than one pathogenic mutation and each one carried at least one pathogenic mutation. The major genes harboring the pathogenic mutations were:
,
,
,
,
,
,
,
,
,
, and
. Thirty-one patients (30.6%) had
mutations and twenty (19.8%) had
mutations. Our results showed that exon 10 and exon 11 harbored 3 and 5 mutations, respectively, in
and
genes. Our analysis also revealed that the
gene significantly co-occurred with each of the
gene (
= 0.003, event ratio 11/21), the
gene (
= 0.01, 4/10), the
gene (
= 0.02, 4/11), and the
gene (
= 0.04, 4/12). In addition, the
gene significantly co-occurred with the
gene (
= 0.01, 3/7). Furthermore, there was a significant mutually exclusive event between the
gene and the
gene (
= 0.04, 1/36). Interestingly, we identified population specific germline mutations in genes showing potentials for targeted therapy to meet the need for incorporating precision oncology into clinical practice. For example, the mutations identified in the
,
, and
genes.
Multi-gene panel sequencing was used to detect the deleterious mutations associated with familial BC, which in turns mitigate the essential need for implementing next generation sequencing technologies in precision oncology to identify cancer predisposing genes. Moreover, identifying DNA repair gene mutations, with focus on non-BRCA genes, might serve as candidates for targeted therapy and will be increasingly used in precision oncology.