The Mutational Spectrum of Pre- and Post-Neoadjuvant Chemotherapy Triple-Negative Breast Cancers
The response of triple-negative breast cancer (TNBC) patients to pre-operative (neoadjuvant chemotherapy) is a critical factor of their outcome. To determine the effects of chemotherapy on the tumor genome and to identify mutations associated with chemoresistance and sensitivity, we performed whole...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-12-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/15/1/27 |
| _version_ | 1797343859826491392 |
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| author | Adriana Aguilar-Mahecha Najmeh Alirezaie Josiane Lafleur Eric Bareke Ewa Przybytkowski Cathy Lan Luca Cavallone Myriam Salem Manuela Pelmus Olga Aleynikova Celia Greenwood Amanda Lovato Cristiano Ferrario Jean-François Boileau Catalin Mihalcioiu Josée-Anne Roy Elizabeth Marcus Federico Discepola Jacek Majewski Mark Basik |
| author_facet | Adriana Aguilar-Mahecha Najmeh Alirezaie Josiane Lafleur Eric Bareke Ewa Przybytkowski Cathy Lan Luca Cavallone Myriam Salem Manuela Pelmus Olga Aleynikova Celia Greenwood Amanda Lovato Cristiano Ferrario Jean-François Boileau Catalin Mihalcioiu Josée-Anne Roy Elizabeth Marcus Federico Discepola Jacek Majewski Mark Basik |
| author_sort | Adriana Aguilar-Mahecha |
| collection | DOAJ |
| description | The response of triple-negative breast cancer (TNBC) patients to pre-operative (neoadjuvant chemotherapy) is a critical factor of their outcome. To determine the effects of chemotherapy on the tumor genome and to identify mutations associated with chemoresistance and sensitivity, we performed whole exome sequencing on pre/post-chemotherapy tumors and matched lymphocytes from 26 patients. We observed great inter-tumoral heterogeneity with no gene mutated recurrently in more than four tumors besides TP53. Although the degree of response to chemotherapy in residual tumors was associated with more subclonal changes during chemotherapy, there was minimal evolution between pre/post-tumors. Indeed, gene sets enriched for mutations in pre- and post-chemotherapy tumors were very similar and reflected genes involved in the biological process of neurogenesis. Somatically mutated genes present in chemosensitive tumors included COL1A2, PRMD15, APOBEC3B, PALB2 and histone protein encoding genes, while BRCA1, ATR, ARID1A, XRCC3 and genes encoding for tubulin-associated proteins were present in the chemoresistant tumors. We also found that the mutational spectrum of post-chemotherapy tumors was more reflective of matching metastatic tumor biopsies than pre-chemotherapy samples. These findings support a portrait of modest ongoing genomic instability with respect to single-nucleotide variants induced by or selected for by chemotherapy in TNBCs. |
| first_indexed | 2024-03-08T10:53:56Z |
| format | Article |
| id | doaj.art-0e7d84274b4e487890fe81187e5fd46f |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-08T10:53:56Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-0e7d84274b4e487890fe81187e5fd46f2024-01-26T16:41:27ZengMDPI AGGenes2073-44252023-12-011512710.3390/genes15010027The Mutational Spectrum of Pre- and Post-Neoadjuvant Chemotherapy Triple-Negative Breast CancersAdriana Aguilar-Mahecha0Najmeh Alirezaie1Josiane Lafleur2Eric Bareke3Ewa Przybytkowski4Cathy Lan5Luca Cavallone6Myriam Salem7Manuela Pelmus8Olga Aleynikova9Celia Greenwood10Amanda Lovato11Cristiano Ferrario12Jean-François Boileau13Catalin Mihalcioiu14Josée-Anne Roy15Elizabeth Marcus16Federico Discepola17Jacek Majewski18Mark Basik19Cancer Genomics and Translational Research Laboratory, Lady Davis Institute, Jewish General Hospital, Montreal, QC H3T 1E2, CanadaDepartment of Human Genetics, McGill University, Montreal, QC H3A 1A4, CanadaCancer Genomics and Translational Research Laboratory, Lady Davis Institute, Jewish General Hospital, Montreal, QC H3T 1E2, CanadaDepartment of Human Genetics, McGill University, Montreal, QC H3A 1A4, CanadaCancer Genomics and Translational Research Laboratory, Lady Davis Institute, Jewish General Hospital, Montreal, QC H3T 1E2, CanadaCancer Genomics and Translational Research Laboratory, Lady Davis Institute, Jewish General Hospital, Montreal, QC H3T 1E2, CanadaCancer Genomics and Translational Research Laboratory, Lady Davis Institute, Jewish General Hospital, Montreal, QC H3T 1E2, CanadaCancer Genomics and Translational Research Laboratory, Lady Davis Institute, Jewish General Hospital, Montreal, QC H3T 1E2, CanadaDepartment of Pathology, Jewish General Hospital, Montreal, QC H3T 1E2, CanadaDepartment of Pathology, Jewish General Hospital, Montreal, QC H3T 1E2, CanadaLady Davis Institute, Jewish General Hospital, Montreal, QC H3T 1E2, CanadaLady Davis Institute, Jewish General Hospital, Montreal, QC H3T 1E2, CanadaDepartment of Oncology, Jewish General Hospital, Montreal, QC H3T 1E2, CanadaDepartment of Oncology, Jewish General Hospital, Montreal, QC H3T 1E2, CanadaMcGill University Health Center, Montreal, QC H3A 3J1, CanadaHôpital du Sacré-Cœur de Montréal, Montreal, QC H4J 1C5, CanadaCook County Hospital, Chicago, IL 60612, USADepartment of Radiology, Jewish General Hospital, Montreal, QC H3T 1E2, CanadaDepartment of Human Genetics, McGill University, Montreal, QC H3A 1A4, CanadaCancer Genomics and Translational Research Laboratory, Lady Davis Institute, Jewish General Hospital, Montreal, QC H3T 1E2, CanadaThe response of triple-negative breast cancer (TNBC) patients to pre-operative (neoadjuvant chemotherapy) is a critical factor of their outcome. To determine the effects of chemotherapy on the tumor genome and to identify mutations associated with chemoresistance and sensitivity, we performed whole exome sequencing on pre/post-chemotherapy tumors and matched lymphocytes from 26 patients. We observed great inter-tumoral heterogeneity with no gene mutated recurrently in more than four tumors besides TP53. Although the degree of response to chemotherapy in residual tumors was associated with more subclonal changes during chemotherapy, there was minimal evolution between pre/post-tumors. Indeed, gene sets enriched for mutations in pre- and post-chemotherapy tumors were very similar and reflected genes involved in the biological process of neurogenesis. Somatically mutated genes present in chemosensitive tumors included COL1A2, PRMD15, APOBEC3B, PALB2 and histone protein encoding genes, while BRCA1, ATR, ARID1A, XRCC3 and genes encoding for tubulin-associated proteins were present in the chemoresistant tumors. We also found that the mutational spectrum of post-chemotherapy tumors was more reflective of matching metastatic tumor biopsies than pre-chemotherapy samples. These findings support a portrait of modest ongoing genomic instability with respect to single-nucleotide variants induced by or selected for by chemotherapy in TNBCs.https://www.mdpi.com/2073-4425/15/1/27triple-negative breast cancerchemoresistancechemotherapygenomicsexome sequencingmutations |
| spellingShingle | Adriana Aguilar-Mahecha Najmeh Alirezaie Josiane Lafleur Eric Bareke Ewa Przybytkowski Cathy Lan Luca Cavallone Myriam Salem Manuela Pelmus Olga Aleynikova Celia Greenwood Amanda Lovato Cristiano Ferrario Jean-François Boileau Catalin Mihalcioiu Josée-Anne Roy Elizabeth Marcus Federico Discepola Jacek Majewski Mark Basik The Mutational Spectrum of Pre- and Post-Neoadjuvant Chemotherapy Triple-Negative Breast Cancers Genes triple-negative breast cancer chemoresistance chemotherapy genomics exome sequencing mutations |
| title | The Mutational Spectrum of Pre- and Post-Neoadjuvant Chemotherapy Triple-Negative Breast Cancers |
| title_full | The Mutational Spectrum of Pre- and Post-Neoadjuvant Chemotherapy Triple-Negative Breast Cancers |
| title_fullStr | The Mutational Spectrum of Pre- and Post-Neoadjuvant Chemotherapy Triple-Negative Breast Cancers |
| title_full_unstemmed | The Mutational Spectrum of Pre- and Post-Neoadjuvant Chemotherapy Triple-Negative Breast Cancers |
| title_short | The Mutational Spectrum of Pre- and Post-Neoadjuvant Chemotherapy Triple-Negative Breast Cancers |
| title_sort | mutational spectrum of pre and post neoadjuvant chemotherapy triple negative breast cancers |
| topic | triple-negative breast cancer chemoresistance chemotherapy genomics exome sequencing mutations |
| url | https://www.mdpi.com/2073-4425/15/1/27 |
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