Germline Variant Spectrum in Southern Italian High-Risk Hereditary Breast Cancer Patients: Insights from Multi-Gene
Valentina Rocca1,2, Elisa Lo Feudo1,2, Francesca Dinatolo1
1Medical Genetics Unit, Renato Dulbecco University Hospital, 88100 Catanzaro, Italy.
Current Issues in Molecular Biology
|November 26, 2024
Summary
Hereditary breast cancer genetic screening in Southern Italy found pathogenic variants in 13% of high-risk patients. Non-BRCA1/2 genes were significant, highlighting the need for population-specific genetic testing.
Area of Science:
- Genetics
- Oncology
- Molecular Biology
Background:
- Hereditary breast cancer (HBC) constitutes 5-10% of all breast cancer cases.
- Germline pathogenic variants in genes like BRCA1/2 are critical in HBC etiology.
- Understanding genetic heterogeneity is key for effective risk assessment and management.
Purpose of the Study:
- To determine the prevalence and spectrum of germline variants in 13 cancer predisposition genes.
- To analyze high-risk hereditary breast cancer patients from Southern Italy.
- To inform population-specific genetic screening strategies.
Main Methods:
- Next-generation sequencing (NGS) was used to analyze germline DNA.
- 254 high-risk individuals were selected based on genetic counseling criteria.
- 13 cancer predisposition genes were analyzed for pathogenic or likely pathogenic variants.
Main Results:
- Pathogenic/likely pathogenic variants were identified in 13% (34/254) of patients.
- Over half (54%) of these variants were found in non-BRCA1/2 genes.
- A recurrent BRCA1 founder mutation (c.4964_4982del) was identified; variants in PALB2, ATM, TP53, CHEK2, RAD51C were also noted.
Conclusions:
- Germline variants in multiple genes contribute to hereditary breast cancer in Southern Italy.
- Population-specific genetic screening, including non-BRCA1/2 genes, is crucial.
- Findings support tailored genetic testing and counseling for precision medicine in oncology.
