Next-Generation Sequencing and Triple-Negative Breast Cancer: Insights and Applications
The poor survival of triple-negative breast cancer (TNBC) is due to its aggressive behavior, large heterogeneity, and high risk of recurrence. A comprehensive molecular investigation of this type of breast cancer using high-throughput next-generation sequencing (NGS) methods may help to elucidate it...
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MDPI AG
2023-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/11/9688 |
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| author | Domenico Tierno Gabriele Grassi Serena Scomersi Marina Bortul Daniele Generali Fabrizio Zanconati Bruna Scaggiante |
| author_facet | Domenico Tierno Gabriele Grassi Serena Scomersi Marina Bortul Daniele Generali Fabrizio Zanconati Bruna Scaggiante |
| author_sort | Domenico Tierno |
| collection | DOAJ |
| description | The poor survival of triple-negative breast cancer (TNBC) is due to its aggressive behavior, large heterogeneity, and high risk of recurrence. A comprehensive molecular investigation of this type of breast cancer using high-throughput next-generation sequencing (NGS) methods may help to elucidate its potential progression and discover biomarkers related to patient survival. In this review, the NGS applications in TNBC research are described. Many NGS studies point to <i>TP53</i> mutations, immunocheckpoint response genes, and aberrations in the PIK3CA and DNA repair pathways as recurrent pathogenic alterations in TNBC. Beyond their diagnostic and predictive/prognostic value, these findings suggest potential personalized treatments in PD -L1-positive TNBC or in TNBC with a homologous recombination deficit. Moreover, the comprehensive sequencing of large genomes with NGS has enabled the identification of novel markers with clinical value in TNBC, such as <i>AURKA</i>, <i>MYC</i>, and <i>JARID2</i> mutations. In addition, NGS investigations to explore ethnicity-specific alterations have pointed to <i>EZH2</i> overexpression, <i>BRCA1</i> alterations, and a <i>BRCA2</i>-delaAAGA mutation as possible molecular signatures of African and African American TNBC. Finally, the development of long-read sequencing methods and their combination with optimized short-read techniques promise to improve the efficiency of NGS approaches for future massive clinical use. |
| first_indexed | 2024-03-11T03:04:22Z |
| format | Article |
| id | doaj.art-1e610edc66e94f4086bc89556d6892d8 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T03:04:22Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-1e610edc66e94f4086bc89556d6892d82023-11-18T08:02:38ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-06-012411968810.3390/ijms24119688Next-Generation Sequencing and Triple-Negative Breast Cancer: Insights and ApplicationsDomenico Tierno0Gabriele Grassi1Serena Scomersi2Marina Bortul3Daniele Generali4Fabrizio Zanconati5Bruna Scaggiante6Department of Life Sciences, University of Trieste, 34127 Trieste, ItalyDepartment of Life Sciences, University of Trieste, 34127 Trieste, ItalyBreast Unit-Azienda Sanitaria Universitaria Integrata Giuliano Isontina ASUGI, University of Trieste, 34149 Trieste, ItalyDepartment of Medical, Surgical and Health Sciences, University of Trieste, 34149 Trieste, ItalyDepartment of Medical, Surgical and Health Sciences, University of Trieste, 34149 Trieste, ItalyDepartment of Medical, Surgical and Health Sciences, University of Trieste, 34149 Trieste, ItalyDepartment of Life Sciences, University of Trieste, 34127 Trieste, ItalyThe poor survival of triple-negative breast cancer (TNBC) is due to its aggressive behavior, large heterogeneity, and high risk of recurrence. A comprehensive molecular investigation of this type of breast cancer using high-throughput next-generation sequencing (NGS) methods may help to elucidate its potential progression and discover biomarkers related to patient survival. In this review, the NGS applications in TNBC research are described. Many NGS studies point to <i>TP53</i> mutations, immunocheckpoint response genes, and aberrations in the PIK3CA and DNA repair pathways as recurrent pathogenic alterations in TNBC. Beyond their diagnostic and predictive/prognostic value, these findings suggest potential personalized treatments in PD -L1-positive TNBC or in TNBC with a homologous recombination deficit. Moreover, the comprehensive sequencing of large genomes with NGS has enabled the identification of novel markers with clinical value in TNBC, such as <i>AURKA</i>, <i>MYC</i>, and <i>JARID2</i> mutations. In addition, NGS investigations to explore ethnicity-specific alterations have pointed to <i>EZH2</i> overexpression, <i>BRCA1</i> alterations, and a <i>BRCA2</i>-delaAAGA mutation as possible molecular signatures of African and African American TNBC. Finally, the development of long-read sequencing methods and their combination with optimized short-read techniques promise to improve the efficiency of NGS approaches for future massive clinical use.https://www.mdpi.com/1422-0067/24/11/9688454-pyrosequencingIlluminaIon Torrentnext-generation sequencingtriple-negative breast cancer |
| spellingShingle | Domenico Tierno Gabriele Grassi Serena Scomersi Marina Bortul Daniele Generali Fabrizio Zanconati Bruna Scaggiante Next-Generation Sequencing and Triple-Negative Breast Cancer: Insights and Applications International Journal of Molecular Sciences 454-pyrosequencing Illumina Ion Torrent next-generation sequencing triple-negative breast cancer |
| title | Next-Generation Sequencing and Triple-Negative Breast Cancer: Insights and Applications |
| title_full | Next-Generation Sequencing and Triple-Negative Breast Cancer: Insights and Applications |
| title_fullStr | Next-Generation Sequencing and Triple-Negative Breast Cancer: Insights and Applications |
| title_full_unstemmed | Next-Generation Sequencing and Triple-Negative Breast Cancer: Insights and Applications |
| title_short | Next-Generation Sequencing and Triple-Negative Breast Cancer: Insights and Applications |
| title_sort | next generation sequencing and triple negative breast cancer insights and applications |
| topic | 454-pyrosequencing Illumina Ion Torrent next-generation sequencing triple-negative breast cancer |
| url | https://www.mdpi.com/1422-0067/24/11/9688 |
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