Molecular profiling of male breast cancer by multigene panel testing: Implications for precision oncology
IntroductionCompared with breast cancer (BC) in women, BC in men is a rare disease with genetic and molecular peculiarities. Therapeutic approaches for male BC (MBC) are currently extrapolated from the clinical management of female BC, although the disease does not exactly overlap in males and femal...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.1092201/full |
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| author | Virginia Valentini Valentina Silvestri Agostino Bucalo Giulia Conti Mina Karimi Linda Di Francesco Giulia Pomati Silvia Mezi Bruna Cerbelli Maria Gemma Pignataro Arianna Nicolussi Anna Coppa Giulia D’Amati Giuseppe Giannini Giuseppe Giannini Laura Ottini |
| author_facet | Virginia Valentini Valentina Silvestri Agostino Bucalo Giulia Conti Mina Karimi Linda Di Francesco Giulia Pomati Silvia Mezi Bruna Cerbelli Maria Gemma Pignataro Arianna Nicolussi Anna Coppa Giulia D’Amati Giuseppe Giannini Giuseppe Giannini Laura Ottini |
| author_sort | Virginia Valentini |
| collection | DOAJ |
| description | IntroductionCompared with breast cancer (BC) in women, BC in men is a rare disease with genetic and molecular peculiarities. Therapeutic approaches for male BC (MBC) are currently extrapolated from the clinical management of female BC, although the disease does not exactly overlap in males and females. Data on specific molecular biomarkers in MBC are lacking, cutting out male patients from more appropriate therapeutic strategies. Growing evidence indicates that Next Generation Sequencing (NGS) multigene panel testing can be used for the detection of predictive molecular biomarkers, including Tumor Mutational Burden (TMB) and Microsatellite Instability (MSI).MethodsIn this study, NGS multigene gene panel sequencing, targeting 1.94 Mb of the genome at 523 cancer-relevant genes (TruSight Oncology 500, Illumina), was used to identify and characterize somatic variants, Copy Number Variations (CNVs), TMB and MSI, in 15 Formalin-Fixed Paraffin-Embedded (FFPE) male breast cancer samples.Results and discussionA total of 40 pathogenic variants were detected in 24 genes. All MBC cases harbored at least one pathogenic variant. PIK3CA was the most frequently mutated gene, with six (40.0%) MBCs harboring targetable PIK3CA alterations. CNVs analysis showed copy number gains in 22 genes. No copy number losses were found. Specifically, 13 (86.7%) MBCs showed gene copy number gains. MYC was the most frequently amplified gene with eight (53.3%) MBCs showing a median fold-changes value of 1.9 (range 1.8-3.8). A median TMB value of 4.3 (range 0.8-12.3) mut/Mb was observed, with two (13%) MBCs showing high-TMB. The median percentage of MSI was 2.4% (range 0-17.6%), with two (13%) MBCs showing high-MSI. Overall, these results indicate that NGS multigene panel sequencing can provide a comprehensive molecular tumor profiling in MBC. The identification of targetable molecular alterations in more than 70% of MBCs suggests that the NGS approach may allow for the selection of MBC patients eligible for precision/targeted therapy. |
| first_indexed | 2024-04-11T00:34:37Z |
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| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-11T00:34:37Z |
| publishDate | 2023-01-01 |
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| series | Frontiers in Oncology |
| spelling | doaj.art-30c1888cb4474392bf22a874b1d7d2592023-01-06T22:18:49ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-01-011210.3389/fonc.2022.10922011092201Molecular profiling of male breast cancer by multigene panel testing: Implications for precision oncologyVirginia Valentini0Valentina Silvestri1Agostino Bucalo2Giulia Conti3Mina Karimi4Linda Di Francesco5Giulia Pomati6Silvia Mezi7Bruna Cerbelli8Maria Gemma Pignataro9Arianna Nicolussi10Anna Coppa11Giulia D’Amati12Giuseppe Giannini13Giuseppe Giannini14Laura Ottini15Department of Molecular Medicine, Sapienza University of Rome, Rome, ItalyDepartment of Molecular Medicine, Sapienza University of Rome, Rome, ItalyDepartment of Molecular Medicine, Sapienza University of Rome, Rome, ItalyDepartment of Molecular Medicine, Sapienza University of Rome, Rome, ItalyDepartment of Molecular Medicine, Sapienza University of Rome, Rome, ItalyDepartment of Molecular Medicine, Sapienza University of Rome, Rome, ItalyDepartment of Molecular Medicine, Sapienza University of Rome, Rome, ItalyDepartment of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Rome, ItalyDepartment of Medical-Surgical Sciences and Biotechnologies Sapienza University of Rome, Rome, ItalyDepartment of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, Rome, ItalyDepartment of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Rome, ItalyDepartment of Molecular Medicine, Sapienza University of Rome, Rome, ItalyIstituto Pasteur-Fondazione Cenci Bolognetti, Rome, ItalyDepartment of Molecular Medicine, Sapienza University of Rome, Rome, ItalyIntroductionCompared with breast cancer (BC) in women, BC in men is a rare disease with genetic and molecular peculiarities. Therapeutic approaches for male BC (MBC) are currently extrapolated from the clinical management of female BC, although the disease does not exactly overlap in males and females. Data on specific molecular biomarkers in MBC are lacking, cutting out male patients from more appropriate therapeutic strategies. Growing evidence indicates that Next Generation Sequencing (NGS) multigene panel testing can be used for the detection of predictive molecular biomarkers, including Tumor Mutational Burden (TMB) and Microsatellite Instability (MSI).MethodsIn this study, NGS multigene gene panel sequencing, targeting 1.94 Mb of the genome at 523 cancer-relevant genes (TruSight Oncology 500, Illumina), was used to identify and characterize somatic variants, Copy Number Variations (CNVs), TMB and MSI, in 15 Formalin-Fixed Paraffin-Embedded (FFPE) male breast cancer samples.Results and discussionA total of 40 pathogenic variants were detected in 24 genes. All MBC cases harbored at least one pathogenic variant. PIK3CA was the most frequently mutated gene, with six (40.0%) MBCs harboring targetable PIK3CA alterations. CNVs analysis showed copy number gains in 22 genes. No copy number losses were found. Specifically, 13 (86.7%) MBCs showed gene copy number gains. MYC was the most frequently amplified gene with eight (53.3%) MBCs showing a median fold-changes value of 1.9 (range 1.8-3.8). A median TMB value of 4.3 (range 0.8-12.3) mut/Mb was observed, with two (13%) MBCs showing high-TMB. The median percentage of MSI was 2.4% (range 0-17.6%), with two (13%) MBCs showing high-MSI. Overall, these results indicate that NGS multigene panel sequencing can provide a comprehensive molecular tumor profiling in MBC. The identification of targetable molecular alterations in more than 70% of MBCs suggests that the NGS approach may allow for the selection of MBC patients eligible for precision/targeted therapy.https://www.frontiersin.org/articles/10.3389/fonc.2022.1092201/fullmale breast cancer (MBC)tumor profilingtargeted gene panel sequencingclinically actionable genetic variantstumor mutational burden (TMB)microsatellite instability (MSI) |
| spellingShingle | Virginia Valentini Valentina Silvestri Agostino Bucalo Giulia Conti Mina Karimi Linda Di Francesco Giulia Pomati Silvia Mezi Bruna Cerbelli Maria Gemma Pignataro Arianna Nicolussi Anna Coppa Giulia D’Amati Giuseppe Giannini Giuseppe Giannini Laura Ottini Molecular profiling of male breast cancer by multigene panel testing: Implications for precision oncology Frontiers in Oncology male breast cancer (MBC) tumor profiling targeted gene panel sequencing clinically actionable genetic variants tumor mutational burden (TMB) microsatellite instability (MSI) |
| title | Molecular profiling of male breast cancer by multigene panel testing: Implications for precision oncology |
| title_full | Molecular profiling of male breast cancer by multigene panel testing: Implications for precision oncology |
| title_fullStr | Molecular profiling of male breast cancer by multigene panel testing: Implications for precision oncology |
| title_full_unstemmed | Molecular profiling of male breast cancer by multigene panel testing: Implications for precision oncology |
| title_short | Molecular profiling of male breast cancer by multigene panel testing: Implications for precision oncology |
| title_sort | molecular profiling of male breast cancer by multigene panel testing implications for precision oncology |
| topic | male breast cancer (MBC) tumor profiling targeted gene panel sequencing clinically actionable genetic variants tumor mutational burden (TMB) microsatellite instability (MSI) |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.1092201/full |
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