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Updated: May 9, 2026
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Identification of Somatic and Germline Mutations Influencing Treatment Outcomes and Disease Susceptibility in
Asma Mehri1,2, Ahmed Baligh Laaribi1,2, Ichraf Jbir1,3,4
1Laboratory of Microorganisms and Active Biomolecules (LR03ES03), Faculty of Sciences of Tunis, University of Tunis El Manar, Tunis, Tunisia.
Abstract:
Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype characterized by marked molecular heterogeneity and limited targeted therapeutic options. Its incidence is rising in many low- and middle-income countries, where genetic profiling of affected patients remains largely unexplored despite evident clinical disparities. This study aimed to characterize, for the first time in a Tunisian cohort, the spectrum of germline and somatic mutations in TNBC patients and to assess their potential impact on therapeutic response. Targeted next-generation sequencing (NGS) of hotspot regions across 50 cancer-related genes was performed in twelve patients using the AmpliSeq for Illumina Cancer Hotspot Panel v2, applied to both tumor tissues and matched adjacent non-tumoral tissues. Bioinformatics analysis revealed recurrent germline variants present in all samples, notably in TP53 (rs1042522), CSF1R (rs2066933), FGFR3 (rs7688609), RET (rs1800861), KDR (rs7692791), and PDGFRA (rs1873778). In tumor tissues, 32 deleterious somatic variants were detected across 20 oncogenes, with TP53 emerging as the most frequently mutated gene (58%). Distinct mutational patterns were observed in relation to treatment response. Notably, the co-occurrence of AKT1 (rs121434592) and TP53 (rs876660754) was observed in a patient with treatment resistance, whereas an in-frame deletion in NOTCH1 (p.Val1578del) was uniquely detected in patients who subsequently experienced disease recurrence. These findings provide the first comprehensive characterization of germline and somatic alterations in Tunisian TNBC patients, representing a North African cohort. They reveal the heterogeneity of mutation patterns linked to treatment response, and emphasize the importance of genomic profiling into clinical practice and guide personalized therapeutic strategies.
Insights
This study reveals genetic mutations in Tunisian triple-negative breast cancer (TNBC) patients. Identifying these germline and somatic alterations can guide personalized therapies for this aggressive cancer subtype.
Area of Science:
- Genomics
- Oncology
- Molecular Biology
Background:
- Triple-negative breast cancer (TNBC) is aggressive and heterogeneous with limited targeted therapies.
- TNBC incidence is rising in low- and middle-income countries, with understudied genetic profiles.
- Clinical disparities in TNBC highlight the need for genomic characterization in diverse populations.
Purpose of the Study:
- To characterize germline and somatic mutations in a Tunisian TNBC cohort.
- To assess the impact of these mutations on therapeutic response.
- To provide the first genomic profile of TNBC in a North African population.
Main Methods:
- Targeted next-generation sequencing (NGS) of 50 cancer-related genes.
- Analysis of tumor and matched non-tumoral tissues from twelve TNBC patients.
- Bioinformatics analysis to identify germline and somatic variants.
Main Results:
- Recurrent germline variants found in TP53, CSF1R, FGFR3, RET, KDR, and PDGFRA.
- 32 deleterious somatic variants detected in 20 oncogenes; TP53 was the most mutated (58%).
- Distinct mutation patterns correlated with treatment response, resistance, and recurrence.
Conclusions:
- This study presents the first comprehensive genomic characterization of TNBC in a Tunisian cohort.
- Identified mutation patterns offer insights into TNBC heterogeneity and treatment response.
- Genomic profiling is crucial for guiding personalized therapeutic strategies in TNBC.
